The purpose of this study was to conduct an overview of systematic reviews (SRs) to appraise the published evidence related to pharmacological interventions after traumatic brain injury (TBI). Searches were conducted with Medline, Embase, PsycINFO, Web of Science, PubMed. 780 retrieved SRs underwent a two-level screening to determine inclusion. Data extracted included participant characteristics, TBI severity, study design, pharmacological interventions, and outcomes. SRs were assessed for methodological quality by using the AMSTAR measurement tool. After removing duplicates, 166/780 SRs published between 1990-2017 were reviewed, 62 of which met inclusion criteria. More than 90 drugs and 22 substance-classes were extracted. Most medications were administered during the acute stage. Mild TBI was included in 3% of the SRs. Physiological outcomes comprised 45% of the SRs, primarily mortality. Activities of daily living (ADLs) outcomes constituted 22% of the SRs followed by cognition (13%) and psychological/behavioral outcomes (13%). Only 7% of the SRs assessed adverse events. Inconsistencies in definitions, methods, and heterogeneity of instruments used to measure treatment response were noted. Only a third of the SRs had high methodological quality. Most SRs had heterogeneous TBI samples, outcomes, or methodologies making it difficult to synthesize findings into recommended guidelines. This study demonstrated a need for adequately powered and rigorous randomized clinical trials (RCTs) to provide generalizable evidence on the effectiveness of pharmacologic interventions for TBI. PROSPERO Registration: CRD42015017355