OBJECTIVE: To provide a systematic review of published interventions for posttraumatic brain injury fatigue (PTBIF). METHODS: PubMed and OneSearch were systematically searched for PTBIF interventions published between January 1, 1989, and March 31, 2019. Search results were evaluated for inclusion based on an abstract and full-text review. Inclusion criteria were (1) an investigation of an intervention, (2) participant sample including individuals with traumatic brain injury (TBI), (3) report of fatigue outcome data among individuals with TBI, and (4) articles available in English, Spanish, French, German, Afrikaans, or Dutch. A risk of bias assessment was conducted on all included publications. RESULTS: The search resulted in 2343 publications, with 37 meeting inclusion criteria for this review. Categories of PTBIF interventions were pharmacological ( n = 13), psychological ( n = 9), exercise-based ( n = 4), complementary alternative medicine ( n = 5), electrotherapeutic ( n = 3), and multimodal ( n = 3). Only methylphenidate, modafinil, and cognitive behavioral therapy interventions included multiple cohorts. Pharmacological and psychological interventions represented the groups with the lowest risk of bias. CONCLUSIONS: This review includes 37 studies, with 21 studies published after 2014. Methylphenidate and melatonin were the only pharmacological agents found to reduce fatigue in randomized controlled trials. Creatine given to children prospectively at onset of injury reduced fatigue at follow-up. Walking and water aerobics were effective exercise interventions in isolated randomized controlled studies. One multimodal study of children after concussion was more effective at reducing fatigue and postconcussion symptoms than community standard of care. Other interventions had equivocal results. Overall, more work remains to understand and develop treatments for PTBIF.