Traumatic brain injury (TBI) is prevalent. Declining mortality has led to increasing survivors with chronic sequalae, including depression. With a lack of guidelines, this review aims to provide a comprehensive, evidence-based summary of the management of depression following TBI. Systematic searches were conducted for quasi-experimental and randomized controlled trials (RCTs) assessing pharmacotherapy, psychological interventions, and transcranial magnetic stimulation (TMS). Databases searched CENTRAL, Medline, Embase, CINAHL, PsycINFO, Web of Science, and ProQuest dissertations. Data extraction and risk-of-bias tools were used. Where possible, outcomes were combined into meta-analyses. 2719 studies were identified. After abstract screening and full-text reading, 34 remained. Prophylactic sertraline significantly reduced the odds of depression (OR (odds ratio) = 0.31 [95%CI (confidence interval) = 0.12 to 0.82]). Meta-analysis of RCT’s showed TMS to have the greatest reduction in depression severity (SMD (Standardized-Mean-Difference) = 2.43 [95%CI = 1.24 to 3.61]). Stimulants were the only treatment superior to control (SMD = −1.03 [95%CI = − 1.6 to −0.47]). Methylphenidate was the most effective pharmacotherapy. Sertraline appears effective for prevention. The efficacy of psychological interventions is unclear. TMS as a combination therapy appears promising. Heterogeneity of study populations and dearth of evidence means results should be interpreted cautiously.