For chronic migraine, onabotulinumtoxin A reduced migraine attacks but increased the risk of adverse effects and treatment discontinuation due to adverse effects. For episodic migraine, approved drugs are effective but increase risk of adverse effects and treatment discontinuation due to adverse effects. Some off-label beta blockers and angiotensin inhibiting drugs are effective without bothersome harms and therefore offer the best benefits-to-harms ratio. We could not determine the long-term (i.e., trials of more than 3 months’ duration), preventive benefits and adherence with drugs. Evidence on improving quality of life was inconsistent across individual drugs. Evidence for individualized treatment decisions is very limited. Future research should examine the role of patient characteristics on drug benefits and safety.