Although the effectiveness of interpersonal psychotherapy (IPT) and cognitive therapy (CT) for major depression has been established, little is known about how and for whom they work and how they compare in the long term. The latter is especially relevant for IPT because research on its long-term effects has been limited. This overview paper summarizes findings from a Dutch randomized controlled trial on the effects and mechanisms of change of IPT versus CT for major depression.Adult outpatients with depression (N=182) were randomly assigned to CT (N=76), IPT (N=75), or a 2-month waitlist control group followed by patient's treatment of choice (N=31). The primary outcome was depression severity. Other outcomes were quality of life, social and general psychological functioning, and scores on various mechanism measures. Interventions were compared at the end of treatment and up to 17 months follow-up.On average, IPT and CT were both superior to waitlist, and their outcomes did not differ significantly from one another. However, the pathway through which change occurred appeared to differ. For a majority of participants, one of the interventions was predicted to be more beneficial than the other. No support for the theoretical models of change was found.Outcomes of IPT and CT did not appear to differ significantly. IPT may have an enduring effect not different from that of CT. The field would benefit from further refinement of study methods to disentangle mechanisms of change and from advances in the field of personalized medicine (i.e., person-specific analyses and treatment selection methods).