Little is known about how psychological treatments work. Research on treatment-induced mediators of change may be of help in identifying potential causal mechanisms through which they operate. Outcome-focused randomised controlled trials provide an excellent opportunity for such work. However, certain conceptual and practical difficulties arise when studying psychological treatments, most especially deciding how best to conceptualise the treatment concerned and how to accommodate the fact that most psychological treatments are implemented flexibly. In this paper, these difficulties are discussed, and strategies and procedures for overcoming them are described.