Caffeine is the most widely consumed psychoactive compound worldwide. Its mechanisms of action are dose-dependent and when caffeine overdosing occurs, neurologic, cardiovascular and renal systems are mainly affected. Serious toxicities such as seizure and cardiac arrhythmias, seen with caffeine plasma concentrations of 15 mg/L or higher, have caused poisoning or, rarely, death. Caffeine concentrations of 80-100 mg/L are considered lethal. The aim of this systematic review is to summarize data regarding suicides by caffeine administration and analyze the controversial role of caffeine assumption and suicidal risk. We followed the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) indications in the identification and selection of studies and reviewed a series of fatal cases due intentional intoxication by caffeine. A total of 36 cases have been identified. Our results suggests caffeine seems to be negatively correlated with suicide. Even if some observations suggested that the consumption of caffeine may have beneficial effects against depression, and as a consequence against suicide risk, more in-depth studies are required. Data obtained from our study could support both clinicians and forensic pathologists in identifying possible unrecognized cases.