Complementary and alternative medicine (CAM) practice has traditionally relied on expert opinion and case examples to evaluate the outcome of a particular therapeutic treatment. Such trials are subject to bias, leading to the formation of erroneous conclusions about the effectiveness of most treatments. This paper reviews the feasibility of n-of-1 trials to better evaluate the clinical and statistical significance of CAM therapies. In particular: (1) problems arising from the use of standard therapeutic trials; (2) the n-of-1 trial and data analysis; (3) clinical use and advantages of the n-of-1 trial in conventional medicine; (4) potential clinical uses of the n-of-1 trial in CAM; (5) preliminary guidelines for the use of the n-of-1 trial in CAM; (6) constraints on the use of the n-of-1 trial in CAM; and (7) ethical issues in the conduct of the n-of-1 trial.