From 2004 to 2006, we used a variety of sampling techniques to survey the amphibians of Savannah National Wildlife Refuge (SNWR), a large protected area straddling the lower portions of the Savannah River on the border between South Carolina and Georgia. We documented 22 amphibian species—15 frogs and 7 salamanders—with a possible 23rd species present. Species richness was lower than what might be expected from amphibian field guides of species inhabiting the adjacent Coastal Plain, likely due to a lack of specialized habitats, such as temporary ponds and upland pine forest. Amphibians occupied a variety of habitats and appeared tolerant of the mildly acidic and low-oxygen conditions of many of the wetlands. Although additional species may be found at SNWR, this initial survey provides a historic baseline for monitoring amphibian populations as areas adjacent to the refuge are disturbed, the climate changes, and multi-use management objectives are implemented within refuge boundaries.