Rigorous evaluation of the effects of biofeedback with clinical populations is necessary, but practical problems often preclude utilization of between-groups experimental designs involving large numbers of clients with clinically relevant problems. Single-case experimental designs provide a viable alternative for answering most research questions. In addition, single-case designs possess several distinct advantages for biofeedback research, including a focus on clinical significance, the use of variability as data not error, unique procedures for establishing generality of findings, and an ability to deal with ethical concerns in clinical research. Basic procedures in the use of single-case experimental designs are described and illustrations in clinical biofeedback research are provided.