Depression is a common complication/co-morbidity in patients with brain tumors. Better understanding of the relationships between brain tumors and depression should lead to improvement in patient care. This paper reviews these relationships in order to direct further study to improve patient care, and hopefully, outcome. Both anatomic and physiological perturbations in the brain are likely involved in the associations between depression and brain tumors. Tumor treatments are also associated with depression. Depression has a significant negative impact on outcome in brain tumor patients. The role of treatment of depression in brain tumor patients has been scantly studied. Further investigation directed to these areas of knowledge deficit should benefit depressed patients with brain tumors.