Over the past 70 years, single-case design (SCD) research has evolved to include a broad array of methodological and analytic advances. In this article, we describe some of these advances and discuss how SCDs can be used to optimize behavioral health interventions. Specifically, we discuss how parametric analysis, component analysis, and systematic replications can be used to optimize interventions. We also describe how SCDs can address other features of optimization, which include establishing generality and enabling personalized behavioral medicine. Throughout, we highlight how SCDs can be used during both the development and dissemination stages of behavioral health interventions.