It is almost certain that the earliest usage of insect repellent is not as much a subject for history but rather prehistory and a very, very old at that, likely predating existence of homo sapiens. Zoologists observed that some primates use various plants, such as citrus (Citrus medica), marigold pepper (Piper marginatum) or angel hair (Clematis dioica), known for its repellent properties in the periods of increased insect activity, rubbing the leaves and other parts of the plants on their fur. Other primates were using local millipedes (Orthophorus dorsovittatis) that contain substantial amount of benzoquinones, also possessing repellent qualities, especially against mosquitoes and ticks. In addition, excavation at Sibudu in South Africa revealed a habitation site more than 40.000 years old, where fossilized reed mattresses covered with leaves have been found. The leaves in question were found to be Cape quince (Cryptocarya woodii), a plant possession essential oils characterized by both pleasant smell and insect repellent properties.

The first modern insect repellents were still using natural ingredients, usually plant-based, such as camphor, cintronella, rosins and turpentine. The first synthetic repellent was a dimethyl phtalate, patented in USA in 1929, follwed by Indalone, patented in 1937. These proved quite effective not only against flies and mosquitoes, but also against chiggers, finding widespread use by Allied troops fighting in the tropical regions of Pacific theatre. Concurrent research led during the Second World War to the development of DEET (N,N-diethyl-3-methylbenzamide) by Samuel Gertler's team working for the United States Department of Agriculture in 1944. It was an important breakthrough, as DEET, introduced to US military in 1946 and to civilian market in 1957 remains one of the principal insect repellents available, showing good efficiency against many species of mosquitoes, flies, fleas, bedbugs, chiggers and ticks.

But between prehistoric times and mid-20th century, people were using many different methods to get rid of annoying and often dangerous insects. One of the most common repellents across Asia and Europe has been tansy (Tanacetum cinerariifolium) containing pyrethrines capable of influencing nervous systems of various insects, making them an effective repellent and insecticide. Its usage reaches back to antiquity and is possibly much older, both in Europe and Asia. Bunches of tansy were commonly hung in houses and farm buildings to protect humans and animals from insects. This herb has been also common used whenever hay-filled mattresses were made in the past. Pyrethrines are concentrated on the seed cases, what also led to the usage dried and crushed flower heads, sometimes mixed with talcum of other similar substance as a common remedy against for body lice and fleas.It is worth noting that the quite popular spiral incense mosquito repellent date back to early 1890s, when they were first introduced by Japanese entrepreneurs Eiichiro and Yuki Ueyama in an attempt to make its usage more convenient (the pyrethrum powder was traditionally burned in a brazier). Initially straight and similar to ubiquitous incense sticks and contained pyrethrum powder, dried and powdered tangerine skin and rice starch. Shortly after, they were made longer and coiled into spiral to prolong the burning time.

Burning waste plant matter to produce smoke is a very old method that is used in some areas of Southeast Asia even until today. Wood and leaves of the aromatic plants, such as mango, coconut, betelnut or wild ginger produce repellent effect comparable to modern synthetic agents, although it comes with an important downsides. The effect subsides shortly after the fire extinguishes, while its usage indoors carries non-negligible health hazards. This, by conjecture, allows us to assume that the similar effect might have been produced in other areas where open fire has been used for cooking and heating, what is an ancient practice but could have been found in less developed rural regions of Europe even in late 19th century. It is also worth noting that any open fire would act as a repellent by itself, as it decreases the moisture in the air and mosquitoes avoid dry areas as they facilitate desiccation of their bodies and impair their chemoreceptors.

One the earliest mentions of insect repellents come from Herodotus (5th century BCE) who noticed that Egyptians living in humid regions tend to apply the oil obtained from ricinus (Ricinus communis) as a fuel for the oils lamps to ward off mosquitoes. This practice might be much older though, as the usage of castor oil as laxative is attested in Ebers Papyrus dated to mid-16th century BCE. The latter contains a note stating that 'natron water' (possibly an aqueous solution of sodium carbonate) used to clean the house will repel fleas. It also contains several other recipes, using plant and animal material, although the details are hard to identify. Burned gazelle's dung was also used to repel insects damaging crops, possibly weevils. Indian Ayurvedic texts, such as Charaka Samhita, compiled around 4th century BCE also recommends usage of locally available plants, especially neem (Azadirachta indica), black pepper, lemongrass and wood of deodar cedar, that were either smeared on the surfaces or burned to fumigate interiors.

Many Hellenic texts suggest usage of olive oil, as evidenced in Aristotle's History of Animals or Theophrastus' Enquiry into Plants (early 3rd century BCE) but also works of Apsyrtos, horsemaster of Empreror Constantine the Great. Although olive oil does not have repellent properties, rubbing it over the skin could have masked kairomones (substances neutral for the producer, but of practical user by other beings) sensed by mosquitoes. Other authors point to the various plants, such as coriander seeds or elecampaane (Inula helenium). Pliny in Historia naturalis and Palladius in De re rustica also mention that the ground cumin seeds are efficient remedy for lice.

Likewise, Geoponika, a copendium of agricultural knowledge completed in 10th century CE in Eastern Roman Empire and drawing heavily by earlier agricultural works, from Pliny to Dioscorides to Vindonius, mentions many ways of repelling insects. The most common way described there appears to be burning various plants, including bay leaves (Laurus nobilis), oregano (Origanum vulgare), black cumin (Nigella sativa), all commonly used in cooking at that time. Another solution was to apply the mixture of vinegar, manna and oil. The latter remedy might have been somewhat effective as acidic vinegar has an antibacterial effect, reducing bacterial metabolites used by mosquitoes to locate animal targets. Of note is also the usage of an attractor rather than repellent, as one of the recipes tells that oleander leaves attract fleas, so one can put them in a place away from the bed to get rid of the parasites.