The promise of a new generation of therapies targeted to address neurobiological mechanisms thought to underlie psychological disorders, particularly depression, using cognitive and behavioral techniques is discussed. Relationships between such neurobehaviorally focused therapies and other psychological and rehabilitative interventions are also discussed. Their potential utility as adjuncts to conventional treatment, and the importance of multi-method assessment in their evaluation are emphasized. Finally, initial data from a neurobehavioral "cognitive control training" (CCT) adjunctive intervention for severe unipolar depression is presented as an extended example. These data suggest that CCT aids in reducing both physiological mechanisms underlying depression as well as depressive symptomatology.