This paper examines the clinical research methodologies used for the evaluation of cleft lip and palate therapies. A survey of clinical reports in the Cleft Palate Journal between 1964 and 1988 revealed that almost all used retrospective methods (96%). The authors examine the merits and biases associated with retrospective evaluation of therapies and compared these to prospective randomized clinical trials. The strengths and weaknesses of clinical trials are discussed in relation to the long-term evaluation of primary surgery in cleft patients. For these to be successful, further work is needed to investigate questions such as sample size, possible predictors of long-term outcome, and improved methods of presurgical assessment. The authors conclude that if the uncertainties associated with the choice of primary cleft surgery are to be resolved, the challenge of multicenter prospective clinical trials must be faced by the various disciplines involved in cleft palate clinical research.