A combination of behavioral and medication-based interventions has been the most effective form of treatment for reducing problem behavior in individuals with intellectual and developmental disabilities. Evaluating the 2 types of interventions in combination and separately may require that researchers adapt methods traditionally used to evaluate drug interventions for individuals without disabilities. Some methodological difficulties that arise when evaluating drug treatments with this population include the withholding of treatment from control groups, identifying large homogeneous samples of participants, predicting individual clinical responsiveness, and many others. The purpose of this article is to summarize the methodological problems that arise when studying drug-behavior interactions among people with intellectual and developmental disabilities and to suggest alternative methods that may ameliorate these issues.