Nesting of patients within therapists in psychotherapy trials creates an additional level within the design. The multilevel nature of this design has implications for the precision, internal and external validity of estimates of the treatment effect. Prior to or during a trial, psychotherapies are allocated to therapists and therapists are assigned to patients such that the therapist becomes part of the causal pathway from the intervention to the patient. It is therefore important to consider not only the relationship between interventions and patients but also relationships between interventions and therapists and between therapists and patients. Research designs comparing the effects of therapeutic approaches, therapist characteristics and packages of the two can be unified by viewing therapists as an important source of variability within psychotherapy outcome studies. Methodological considerations arising from therapist variation will be discussed, drawing together and building upon the associated psychotherapy and statistical literatures. Parallels will also be made with related designs and methods of analysis.