The mouth of the Don River has been of great commercial and cultural importance since the ancient times. It was the site of the Greek colony Tanais, of the Genoese fort Tana, and of the Turkish fortress Azak. (See the article on Azov for detailed information on those settlements.) Rostov-on-Don was founded on December 15, 1749, as a customs house was set up on the Temernik River (a tributary of the Don) to control the trade with Turkey. The custom house was built according to the edict of the Empress Elizabeth, the daughter of Peter the Great. Not far from the customhouse grew the fortress. It was named after Russian metropolitan, Saint Dimitry of Rostov, a newly-glorified bishop from the old Northern town Rostov the Great. Later the name was changed to Rostov (in 1806) and then to Rostov-on-Don. As Azov gradually declined, a settlement near the new fortress superseded it in importance as a chief commercial centre of the region. In 1756 the "Russian commercial and trading company of Constantinople" set up there, establishing a settlement on the high bank of the Don known as the "Kupecheskaya Sloboda" ("The merchants' settlement"). In 1796 this settlement received town rights and was renamed Rostov-on-Don, in order to distinguish it from its ancient namesake.

http://en.wikipedia.org/wiki/Rostov-on-Don