This special issue of Evaluation and the Health Professions is dedicated to methods for causal mediation analysis in Single Case Experimental Designs (SCEDs). Mediation analysis is used to identify intermediate variables that transmit the effect of the independent variable on the outcome. Until recently, mediation analysis was mostly confined to between-subjects designs and panel studies with few exceptions. Consequently, most of the developments in causal mediation analysis have also been restricted to such designs. In applied health research, SCEDs have been used to evaluate total effects of treatments on outcomes of interest. Providing researchers with the methods for evaluating causal indirect effects for individual participants can lead to important improvements in diagnosis, treatment, and prevention. This special issue includes articles that describe advanced quantitative methods for testing mediators in SCEDs, propose and test approaches that allow for relaxing statistical assumptions that may not hold in real data, and illustrate mediation analysis for a single participant in real and simulated SCEDs data.