It is one of the most important wintering area for ducks and the largest remaining tract of contiguous bottomland hardwood forest on the North American continent.

The Cache River NWR has gradually expanded to its present size through acquisition from private owners of land.

The long-term goal is to re-forest former farming areas with native vegetation along the meandering sloughs, oxbow lakes, swamps, and bald cypress forests of the Cache River and Bayou De View.

The Cache River NWR already preserves the largest tract of contiguous bottomland hardwood forest remaining in the United States.

On April 29, 2005, a team from Cornell Lab of Ornithology claimed they had taken a four-second video and recorded audio calls of the ivory-billed woodpecker, believed extinct for 60 years, in the refuge.

The boundaries of the area proposed by acquisition include 287,574 acres (116,377 ha) within which land would be purchased from willing buyers and subject to the availability of funds.

Secondly, the FWS proposes to purchase 32,600 acres to extend the refuge about 30 miles northward in a narrow strip, now only six percent forested, along Bayou DeView.

Unique to the Lower Valley of the Mississippi River about 13 percent of this area consists of sand dunes with vegetation adapted to dryer climates.