The U.S. Fish and Wildlife Service, in conjunction with the Alabama Department of Conservation and Natural Resources and the Geological Survey of Alabama, selected the river systems of the five major HUC 4 subregions in Alabama to focus conservation activities for managing, recovering,and restoring populations of rare fishes, mussels, snails, and crayfishes.

HUC 4 Subregions

 Middle Tennessee - Elk
The Tennessee River begins in Virginia, flows south and dips into Alabama, and ends in Kentucky where it joins the Ohio River. This subregion is 10,355 mi2 in size and contains the major tributaries of Bear Creek, Cypress Creek, Limestone Creek, Shoal Creek, Flint River, and the Paint Rock River. The Highland Rim physiographic section makes up the majority of this subregion which results in the highest concentration of karst in the state.

Mobile - Tombigbee
The Mobile - Tombigbee subregion in the Cumberland Plateau and Fall Line Hills physiographic sections falls in Mississippi and Alabama and is 21,889 mi2. Major waterways in this basin include the Black Warrior River, Sipsey River, North River, Locust Fork, and the Tombigbee River. The manmade channel that connects the Tennessee River drainage to the Tombigbee River draining is the Tennessee – Tombigbee Waterway, also known as the Tenn – Tom. It is an important navigational route for barge traffic to reach the Gulf of Mexico. This subregion, as well as the Alabama River subregion, drains into the highly productive and diverse Mobile Delta.

Alabama River
The Alabama River subregion begins in Georgia and ends in Alabama in the Mobile Delta. Covering 22,655 mi2, the Alabama River subregion includes the Coosa River,Tallapoosa River, and the Cahaba River. The rivers have higher minerality and clarity than those of the Cumberland Plateau and the Coastal Plain because of the Valley and Ridge and the Piedmont physiographic features. A large number of manmade reservoirs pepper the basin and are known for quality fishing opportunities.

Choctawhatchee - Escambia 
The Choctawhatchee – Escambia subregion is entirely in Alabama's Coastal drainage system and flows into the Gulf of Mexico. It is 14,342 mi2 in size and includes the Conecuh River,Murder Creek, Pea River, and Choctawhatchee River. This region can be identified by
the rolling hills, slow and muddy to sandy bottom streams, and broad alluvial floodplains.

The Apalachicola River subregion is 20,198 mi2 and falls in Georgia, Florida, and Alabama.
Main rivers that flow through this watershed include the Apalachicola River, Chipola River, and
Uchee Creek. This subregion begins in the Apalachian Mountains and ends in the Gulf of Mexico.