Unipolar depression is one of the most disabling and costly medical illnesses in the world (Lancet Global Mental Health Group et al., 2007; Moussavi et al., 2007). Cognitive behavioral therapy (CBT), a widely studied and taught psychotherapeutic treatment for depression, is among the recommended evidence-based treatments. Although CBT and other treatments are largely effective, many depressed individuals do not fully respond to treatment, leaving them vulnerable for relapse and poor outcomes over the lifespan. This article explores the integration of Motivational Interviewing (MI) as one possible strategy of enhancing CBT outcomes. MI provides an evidence-based approach to addressing motivation for treatment and emphasizing key therapist-client interactional factors that have been linked to clinical outcomes. As such, it may be synergistic with specific aspects of CBT, such as enhancing therapeutic alliance, motivation, and specifically addressing ambivalence/resistance affecting treatment engagement, retention and adherence to various aspects of the treatment (such as homework). For clinicians learning CBT, MI may also provide a specified model for learning basic psychotherapeutic skills such as empathy, collaboration, and client-centered active listening. Given the urgency of improving the potency of depression treatments, the extent to which the blending of a MI with CBT will improve the overall effectiveness is worthy of clinical research.