Life review has been established as an evidence-based treatment for depression and anxiety. This paper addresses an important gap in the existing evidence of the working mechanisms of life review. We were able to longitudinally investigate possible mediators of a life-review intervention on depression and anxiety in the context of a large randomized controlled trial. A total of 202 older Dutch adults living in the community participated in this study. They were randomly assigned to either life review or care as usual. Participants were measured in terms of their depressive and anxiety symptoms, reminiscence functions, meaning in life, mastery and positive thoughts at study entry (t0), postintervention (t1; 3 months after study entry), and follow-up (t2; 3 months after the end of the intervention). Findings suggest that processes which have been theoretically and empirically proposed as important processes of change in life review therapy, that is, bitterness revival and boredom reduction reminiscence, mastery and positive thoughts, are indeed mediating the effects of life review on depression and anxiety. It is now recommended to measure these processes during the intervention in order to shed light on the exact process of change and direction of causality.