Lostwood NWR lies in the heart of the Missouri Coteau region, an ancient glacial moraine area. This is an area of rolling hills covered with mixed-grass prairie. The area is dotted with wetlands, commonly called "potholes". The refuge contains a 5,577 acre Wilderness Area established in 1975.
The refuge provides breeding habitat for the Great Plains population of the threatened Piping Plover. The refuge is also a stronghold of declining grassland species, such as Baird's Sparrow, Sprague's Pipit, Le Conte's Sparrow, and Nelson's Sparrow. It is also an important breeding area for waterfowl and prairie shorebirds.
Using prescribed burning and grazing, previous refuge staff have slowly restored the native mixed-grass prairie. However, recent staff changes and insufficient resources threaten to undo the accomplishments of the past 30 years.