I can only really talk about the Ottoman period:

Until 1524, the Ottomans didn't really utilize the Danube. The reason for that was not the fact that the river was a border, but the fact that they didn't master sailing through the Iron Gate. Even later, one could travel through the gorge only between May and November. The river didn't have a great significance in Ottoman war plans: even though some boats were used in siege of Vienna in 1529, in the second siege there were no such attempts. However, the Ottoman strived to attain key positions on the Danube inside their own territory.

The Ottomans conquered whole flow of the Danube between Esztergom and the Black Sea in 1541. As the Danube soon became the most important inland waterway in European part of the empire, soon the Captaincy of the Danube was founded. The Captain of the Danube (Tuna kapudanı) was in charge for all matters concerning sailing the river. He had two deputies: one was in charge for the flow between Buda and Vidin, while the other one was in charge for the flow downstream of Vidin. When the Ottomans lost most of Hungary (1699), only the second one remained.

From the times of Sultan Mehmed II (1451-1481) light fleet on lower Danube served as support of Ottoman infantry. In 1699 the Danube Fleet had these ships: 19 kalite (ships that can transport ~220 soldiers and has a cannon on its forecastle), 5 big and 18 small firkate (boats with oars that could transport up to 80 soldiers), 3 şayka (ships that can transport 20-50 soldiers, armed with three cannons) and 100 üstüaçık (barges unique to Ottoman Danube; these barges had a long spine with flat bottom made of riveted planks; occassionally they had a sail as well; at the beginning of the 17th century these ships costed ~132 kuruş, while their cost at the end of the 18th century was ~183 kuruş; these barges served as means to transport various kinds of material; they proved so important that the Ottoman administration created a position of the açıklar ağası, who was commander of all such sails and who answered to the Captain of the Danube directly).

Main places for construction of vessels were: Rushchuk, Nicopolis, Vidin, Golubac, Smederevo, Mohacs, Buda and Esztergom. Vessels built in Zvornik, Kruševac and Požega were also used primarily in the Danube. Rushchuk served as the winter base for most of the fleet.

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Thanks to the Capitulations of 1535, France was free to use the Danube and arm her ships on the river against the pirates. Turkish sailors managed to cross the Iron Gates and trade on both sides of the gorge, bringing great ammount of wealth to autonomous princedoms of Wallachia and Moldavia, making them Garden of Istanbul. The gorge had its own administrator (Girdap ağası); at the beginning this was just another title of the Captain of the Danube, but then it was given to the Voyvode of Wallachia, and finally to the administrator of Kladovo. These men were responsible if a ship going through the Iron Gate was attacked by pirates, hit one of numerous rocks in the gorge, or stranded. The ships were transported through the gorge by Christians who got partial tax exemption in exchange for this service (cerahorlar). They controlled the ships using ropes on the coast.

Five ships served this purpose in the half of the 18th century, carrying 150 qualified and 84 unqualified workers.

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Evliya Çelebi wrote that Danube frequently froze during the winter and that this brought wealth to inhabitants of Belgrade: Considering that when the ice 10 hands deep forms, (the administration) doesn't tax imports and selling the imported goods (= bâdž­ü bazâr), at that time a hundred of carriages comes, so everybody, be he poor or priviledged, makes money from trade. All poor become rich. The inhabitants of settlements on shores of the Danube frequently went to boats to trade. Evliya Çelebi wrote that the trees surrounding the river were as tall as mountains.

A lot of ships were for military purposes, but most of the ships were the aforementioned üstüaçıks, which mainly supplied major storehouses and granaries in Belgrade. The storehouses of Belgrade were the main store for munitions and provisions during the entire 17th century. Each Danubian port had its own storehouses, but each of them supplied Belgrade as well (even the Black Sea ports occasionally supplied Belgrade).

Each of these ports on the Danube was also a trading hub. The Ottoman Empire had a smoothly functioning chain of menziler, i.e. way stations on dry land. The Danube ports did not only feature a regular menzil, but also another one, serving those who sail along the Danube. These stations supplied the travelers with kayık**lar (boats), cerahor (mainly Christians that would take care about thhe ship's safety, see my previous post), ulaklar (messengers) and food.

The route Belgrade-Hisarcık-Smederevo-Oršova-Demir Kapı (Iron Gate) -Fethulislam-Vidin-Lomgrad-Nicopolis-Svištov-Rushchuk came to be a route commonly used by diplomats. The first one to use it (that I know of) was Sir William Hussey (1691). The provisioning documents (tayin) of English and Dutch embassies show that the diplomats had right to take wood, hay, 200 cerahor, steersmen and ulaklar at every menzil. Habsburg ambassadors were usually getting more, and they usually praised the Ottomans (especially during first decades, when the Ottoman sailors had to sail upstream and take them by şaykalar, as Habsburg ships were unsuitable for the Iron Gate.

The population around the Danube wasn't just transporting goods downstream and upstream, but also across the continent. Wallachia was a huge exporter of salt and fish. The Voyvode of Wallachia gathered tax on trade of salt from both shores (in exchange for a fixed tribute). Hides and tissues were widely traded along and across the river, as well as tobacco from the 17th century onwards.

Fishing was such a big thing that Sultan Suleyman issued a decree in 1560, declaring all revenues from the islands in the Danube, as well as the marshes and estuaries connected to the river, a part of sultan's hass.