: The incidence of depression is rising worldwide, possibly due to urban crowding and insufficient resources. This pandemic raises the possibility that disabling depression among patients with cancer will increase. Already, about one-third of patients with cancer present with depression. Although many progressive cancer centers are instituting psychooncology services, the projected decline in numbers of psychiatrists in the coming decade suggests that these programs may flounder unless nurses are able to provide adjuvant support. Consequently, this article describes the theoretical and emerging research data base regarding the treatment of cancer-related depression with cognitive-behavioral therapy. Implications drawn from this review suggest that nurses can take an active role in preventing and managing cancer-related depression in direct care environments by developing critical pathways for screening, prevention, treatment, and outcomes assessment using theory-based research.