Aim To conduct an overview of systematic reviews and meta-analyses to summarize the ever-growing evidence on drug use during advanced life support. Methods We searched Embase, Medline, Cochrane central register of controlled trials and Web of science for systematic reviews and meta-analyses reporting on drug use during advanced life support from inception to March, 2020. Two reviewers independently assessed all abstracts for eligibility, extracted data and assessed risk of bias using the AMSTAR-2 tool. Corrected covered areas were calculated from publication citation matrices to account for potential risk of bias. Data were graphically represented using forest plots. Results Twenty-two head-to-head drug comparisons from 47 included articles were analysed. Adrenaline significantly increases the incidence of return of spontaneous circulation and survival to hospital discharge, but not the incidence of neurological intact survival. Vasopressin alone or in combination with adrenaline is not superior to adrenaline alone. There is a trend favouring lidocaine over amiodarone in shockable cardiac arrest. The risk of bias assessment of included studies ranged from very low to very high and the overlap between articles was moderate to high. Conclusions In line with the guidelines, we currently suggest that a standard dose of adrenaline should be administered during resuscitation, however, studies assessing lower doses of adrenaline are pressing. There is no rationale for the combination of vasopressin and adrenaline or vasopressin alone instead of adrenaline. In addition, lidocaine is a valuable alternative for amiodarone and maybe even preferable for shockable cardiac arrest. However more research is necessary.