Metformin has been the cornerstone of the medical management of type 2 diabetes mellitus (T2DM) for over 6 decades now since its first-ever discovery. Although there were initial concerns about its efficacy and safety, increasing evidence over the years proved it to be very effective and safe. It has stood the test of time, proving to be much safer than other drugs in the same class and garnering robust evidence in cardiovascular safety. In patients with T2DM, metformin lowers mean glycated hemoglobin (HbA1c) levels by 1.1–1.2% as monotherapy, by 0.6–0.83% as an add- on therapy to insulin, and by 0.9- 0.95% as add-on therapy to other oral agents. Recently its use has also been explored for unlicensed indications other than diabetes, including but not limited to obesity, polycystic ovarian syndrome (PCOS), and type 1 diabetes. Metformin is also currently under investigation for its role as a cancer adjuvant therapy. We aim to provide a comprehensive review of the available evidence for the safety and efficacy of metformin.