This review aims at presenting an overview on metformin effects in diabetic and pre-diabetic states as well as in Polycystic Ovary Syndrome. The molecular mechanisms in which metformin is involved are discussed in depth. Particular attention is paid to the metabolic alterations and infertility which are important aspects characterizing PCOS. The part devoted to the molecular mechanisms underlying the metformin activity is a necessary introduction to the following sections and helps explaining its therapeutic activity in disorders where the common denominator is insulin resistance. The review also compares the effects of metformin with those of other therapeutic molecules. An important part is also dedicated to the side effects and limitations in the use of this drug, with a particular attention to the long-term effects. Metformin exerts multiple activities at the molecular level, still partly to be clarified, and induces a number of side effects. For these reasons, it should be administered with caution and always under careful control to patients suffering from diabetic and pre-diabetic states, and from PCOS. Furthermore, wherever possible it would be necessary to prefer the use of safer molecules.