Metformin is the most commonly prescribed medication for type 2 diabetes (T2DM) in the world. It has primacy in the treatment of this disease because of its safety record and also because of evidence for reduction in the risk of cardiovascular events. Evidence has accumulated indicating that metformin is safe in people with stage 3 chronic kidney disease (CKD-3). It is estimated that roughly one-quarter of people with CKD-3 and T2DM in the United States (well over 1 million) are ineligible for metformin treatment because of elevated serum creatinine levels. This could be overcome if a scheme, perhaps based on pharmacokinetic studies, could be developed to prescribe reduced doses of metformin in these individuals. There is also substantial evidence from epidemiologic studies to indicate that metformin may not only be safe, but may actually benefit people with heart failure (HF). Prospective, randomized trials of the use of metformin in HF are needed to investigate this possibility.