Outcome research on the efficacy of acceptance and commitment therapy (ACT) has established it as an evidence-based cognitive-behavioral approach in treatment of depression. Mediational and related research, however, has provided mixed support for the sensitivity and specificity of ACT’s purported processes of therapeutic change according to model of psychological flexibility on which it is based. Whether an emerging idionomic approach to process-based interventions, such as ACT for depression that is more tailored to the lived experiences of individual clients enhances its efficacy, while also providing a more coherent understanding of its mechanisms of action, is currently an unanswered empirical question.