Despite a checkered history peppered with delays, uncertainties, and dead ends, as well as fortuitous accidents, metformin has come to assume prominence. It is a drug, with folklore origins, whose clinical benefits are reasonably well defined but one whose mechanism of action continues to resist precise definition. That is not to say that it is prescribed only to a select few or that it is a compound of such structural sophistication that it is intrinsically challenging as an object of research because that is not the case. Metformin is the current standard of care for the treatment of one of the most common chronic conditions in the modern world – type 2 diabetes – and its structure is remarkably simple by comparison with that of most other drugs. It is a modest methylated biguanide (dimethylbiguanide, alias N,N-dimethylimidodicarbonimidic diamide; Figure 9.1) with a molecular weight (165.6 daltons) and structural complexity no greater than that of sugar (glucose; molecular weight 180.3 daltons). Two of the many baffling aspects of the metformin story are the haphazard way in which it first got noticed and the fact that it came to assume the standing it now has at very different times – measured in decades – in different parts of the developed world. Unforeseen too is the extent to which its applications have since expanded from the treatment of type 2 diabetes to the treatment of prediabetes and polycystic ovary syndrome (PCOS), and even cancer.