The purpose of this article is to examine issues pertinent to the study of the clinical effectiveness of manual therapy. The need for complete operational definitions of treatment procedures, criteria for altering treatment, and criteria for subject selection is discussed. The need for studies that examine the relationship among impairment, functional limitations, and disability is also discussed. Considerations for selecting relevant outcome measures are presented. The use of a clinical decision-making model to direct the design of clinical studies on manual therapy is described. This article concludes with a discussion of alternative ways for clinicians to contribute to the manual therapy literature.