Polypharmacy is the concurrent use of multiple medications, including both psychotropic and non-psychotropic drugs. Although it may sometimes be clinically indicated, polypharmacy can have a number of negative consequences, including medication nonadherence, adverse drug reactions, and undesirable drug–drug interactions. The objective of this paper was to gain a better understanding of how to study polypharmacy among people with intellectual and developmental disabilities (IDD). To do this, we reviewed literature on polypharmacy among the elderly and people with IDD to inform future research approaches and methods on polypharmacy in people with IDD. Results identified significant variability in methods used to study polypharmacy, including definitions of polypharmacy, samples studied, analytic strategies, and variables included in the analyses. Four valuable methodological lessons to strengthen future polypharmacy research in individuals with IDD emerged. These included the use of consistent definitions of polypharmacy, the implementation of population-based sampling strategies, the development of clinical guidelines, and the importance of studying associated variables.