Technology-based interventions to promote health are expanding rapidly. Assessing the preliminary efficacy of these interventions can be achieved by employing single-case experiments (sometimes referred to as n-of-1 studies). Although single-case experiments are often misunderstood, they offer excellent solutions to address the challenges associated with testing new technology-based interventions. This paper provides an introduction to single-case techniques and highlights advances in developing and evaluating single-case experiments, which help ensure that treatment outcomes are reliable, replicable, and generalizable. These advances include quality control standards, heuristics to guide visual analysis of time-series data, effect size calculations, and statistical analyses. They also include experimental designs to isolate the active elements in a treatment package and to assess the mechanisms of behavior change. The paper concludes with a discussion of issues related to the generality of findings derived from single-case research and how generality can be established through replication and through analysis of behavioral mechanisms.