The understanding and treatment of depression that develops following traumatic brain injury (TBI) is still unclear and likely to be the result of a complex variety of interacting factors. Past researchers have developed ways to classify important variables related to patients' depression into broad domains such as: Pre-injury assets and liabilities, the nature and severity of brain injury; and reaction to difficulties. However, a better conceptualization of the problem is required in order to guide the assessment and treatment considerations for depressed patients with TBI. This review provides this conceptualization by postulating six theoretical relationships between depression and TBI. The degree of empirical support provided in the literature for these links is indicated. Research findings suggested that an individual with TBI is the most susceptible to depression when any of the following conditions exist: a pre-existing psychiatric disturbance is exacerbated; the injury sustained involved the left anterior region of the brain; and when her individual has poor insight into her deficits, attempts to resume her pre-injury roles and experiences significant failure. For each relationship, a likely outcome is predicted if the recommended treatment plan is not conducted. The present conceptualization and treatment considerations will be of substantial benefit to clinicians working in the area.