A general class of single-case statistical procedures, derived from previously developed nonparametric randomization tests, is presented. These procedures are widely applicable in behavioral and educational research contexts in which only a few experimental “units” (individuals, small groups, or classrooms) are the recipients of one or more experimental treatments or interventions. Specifically illustrated are designs that focus on both the general and comparative effectiveness of alternative interventions (including control/placebo treatments), multiple units with differentiable characteristics (i.e., intervention by unit characteristic interactions), and multiple outcome measures (i.e., intervention by outcome measure interactions). Also provided are operational modifications that enhance the internal validity of studies incorporating single-case randomization-based analyses. Appropriate cautions and issues surrounding the use of these procedures are included.