The Alabama River system, comprising the Alabama, Coosa, and Tallapoosa subsystems, forms the eastern portion of the Mobile River drainage. Physiographic diversity and geologic history have fostered development in the Alabama River system of globally significant levels of aquatic faunal diversity and endemism. At least 184 fishes are native to the system, including at least 33 endemic species. During the past century, dam construction for hydropower generation and navigation resulted in 16 reservoirs that inundate 44% of the length of the Alabama River system main stems. This extensive physical and hydrologic alteration has affected the fish fauna in three major ways. Diadromous and migratory species have declined precipitously. Fish assemblages persisting downstream from large main-stem dams have been simplified by loss of species unable to cope with altered flow and water quality regimes. Fish populations persisting in the headwaters and in tributaries to the mainstem reservoirs are now isolated and subjected to effects of physical and chemical habitat degradation. Ten fishes in the Alabama River system (including seven endemic species) are federally listed as threatened or endangered. Regional experts consider at least 28 additional species to be vulnerable, threatened, or endangered with extinction. Conserving the Alabama River system fish fauna will require innovative dam management, protection of streams from effects of urbanization and water supply development, and control of alien species dispersal. Failure to manage aggressively for integrity of remaining unimpounded portions of the Alabama River system will result in reduced quality of natural resources for future generations, continued assemblage simplification, and species extinction.