In developed countries, Traumatic Brain Injury (TBI) affects approximately 12% of adults, and men are significantly more likely to sustain a TBI than women. Data are presented that document the differential adverse impact of TBI on hospitalization and death rates of men. Data are also presented on the differential effects of TBI on intimate relationships of men and women with a special focus on marital dissolution. Two large national studies in the US showed that the divorce rates of men are markedly higher for men than women. TBI should be conceptualized as a disease that affects families for it has long been known that caregivers carry a significant burden and suffer their own depression, anxiety, and relationship discord. A conceptual analysis of the treatment outcome literature with TBI patients and their caregivers led us to the concerning conclusion that there is a crucial need for treatment outcome trials with both patients and caregivers. Promising emerging evidence from controlled trials suggests that problem-solving therapy and relationship therapy with TBI patients and their caregivers should be treatment priorities with replications and extensions.