Climate change threatens biodiversity globally, yet it can be challenging to predict which species may be most vulnerable. Given the scope of the problem, it is imperative to rapidly assess vulnerability and identify actions to decrease risk. Although a variety of tools have been developed to assess climate change vulnerability, few have been evaluated with regard to their suitability for certain taxonomic groups. Due to their ectothermic physiology, low vagility, and strong association with temporary wetlands, reptiles and amphibians may be particularly vulnerable relative to other groups. Here, we evaluate use of the NatureServe Climate Change Vulnerability Index (CCVI) to assess a large suite of herpetofauna from the Sand Hills Ecoregion of the southeastern United States. Although data were frequently lacking for certain variables (e.g., phenological response to climate change, genetic variation), sufficient data were available to evaluate all 117 species. Sensitivity analyses indicated that results were highly dependent on size of assessment area and climate scenario selection. In addition, several ecological traits common in, but relatively unique to, herpetofauna are likely to contribute to their vulnerability and need special consideration during the scoring process. Despite some limitations, the NatureServe CCVI was a useful tool for screening large numbers of reptile and amphibian species. We provide general recommendations as to how the CCVI tool's application to herpetofauna can be improved through more specific guidance to the user regarding how to incorporate unique physiological and behavioral traits into scoring existing sensitivity factors and through modification to the assessment tool itself.