In some areas of research, such as microgravity life sciences, both the number of subjects and the opportunity for repeated observation under experimental conditions are limited. Small N study designs are appropriate for these situations since they require few subjects and few observations in the experimental condition. Small N studies compare treatment conditions separately for each subject so that between-subject variability does not obscure treatment effects. Multiple observations are collected for each individual in the baseline condition to ensure a stable reference point for comparison with the smaller number of observations collected under the experimental conditions. Individual differences can be overlooked in large N studies, but in small N studies the focus is on the individual, and differences observed between particular individuals can be suggestive of underlying causal processes. We present a step-by-step approach to designing and conducting a small N study.