Major depressive disorder (MDD) represents a key contributor to the global burden of mental illness given its relatively high lifetime prevalence, frequent comorbidity, and disability rates. Evidence-based treatment options for depression include pharmacotherapy and psychotherapy, such as cognitive behavioral therapy (CBT). Beyond traditional CBT, over 15years ago, Hayes proclaimed a new generation of contextualistic and process-orientated so-called third wave of CBT interventions, including acceptance and commitment therapy (ACT). Using mindfulness and acceptance as well as commitment and behavior change processes, the transdiagnostic ACT approach aims to increase psychological flexibility as universal mechanism of behavior change and to build a value-driven orientation in life. ACT for MDD can be provided as either stand-alone individual, group, or self-help formats (e.g., apps) or combined with other approaches like behavioral activation. To date, a steadily growing empirical support from outcome and process research suggests the efficacy of ACT, which appears to work specifically through the six proposed core processes involved in psychological flexibility, such as defusion. In view of an ongoing interest of clinicians in "third-wave" CBTs and the important role of clients' preferences in providing therapy choices that work, the purpose of this chapter is to give a brief overview on the application of ACT in the treatment of MDD in adults.