The sandhills are characterized by continuous grass and forb-covered dunes and swales and are considered to be the largest body of sand in the world that is not a desert. Where the swales dip below the water table, sub-irrigated meadows, marshes, and lakes have formed. In most cases, no stream systems exist between wetlands. Many lakes are maintained solely by underground water sources.

The 45,849-acre Refuge is largely grasslands dotted with hundreds of permanent, semipermanent, and temporary wetlands. It is administered by the U.S. Fish and Wildlife Service (Service) as part of the Crescent Lake/North Platte National Wildlife Refuge Complex. The Complex headquarters is 100 miles to the west in the city of Scottsbluff, Nebraska.

The Refuge contains about 8,251 acres of wetlands. Manipulation of water levels is possible on nine of the lakes and is used to control shoreline vegetation in order to create open shoreline for migratory birds.

Hayden's penstemon, also known as blowout penstemon, is Nebraska's rarest plant and is the only endangered plant on the Refuge. This plant is unique in that it depends on non-vegetated sand surfaces, or blowouts, for its existence. Reactivation of some blowouts has been attempted and seedlings from the University of Nebraska have been transplanted to historic sites.

In 1972, 24,502 acres of the Refuge were proposed for inclusion in the National Wilderness Preservation System. Congress has not acted on that proposal. In the intervening years, the area has been managed to maintain and improve the wilderness characteristics that existed at the time of the proposal.