Single-case experimental designs (SCEDs) represent a family of research designs that use experimental methods to study the effects of treatments on outcomes. The fundamental unit of analysis is the single case-which can be an individual, clinic, or community-ideally with replications of effects within and/or between cases. These designs are flexible and cost-effective and can be used for treatment development, translational research, personalized interventions, and the study of rare diseases and disorders. This article provides a broad overview of the family of single-case experimental designs with corresponding examples, including reversal designs, multiple baseline designs, combined multiple baseline/reversal designs, and integration of single-case designs to identify optimal treatments for individuals into larger randomized controlled trials (RCTs). Personalized N-of-1 trials can be considered a subcategory of SCEDs that overlaps with reversal designs. Relevant issues for each type of design-including comparisons of treatments, design issues such as randomization and blinding, standards for designs, and statistical approaches to complement visual inspection of single-case experimental designs-are also discussed.