Type 2 diabetes mellitus is a progressive disease characterized by persistent insulin resistance and a relentless decline in insulin secretion that is accelerated by chronic hyperglycemia. Mounting evidence indicates that earlier introduction of insulin therapy may mitigate the deleterious effects of glucotoxicity in patients with early type 2 diabetes, presumably by reducing strain on pancreatic beta-cells and enhancing insulin secretion and also by improving peripheral insulin action. At present, the available data can only be considered hypothesis-generating, but support the notion that beginning basal insulin supplementation immediately after combination oral agents fail to attain glycemic targets has the potential to preserve beta-cell integrity or delay beta-cell loss, leading to more sustained glycemic control. Long-term controlled studies are clearly warranted to confirm this treatment paradigm. In the meantime, the tools for translating this concept to clinical practice can be extrapolated from the Treat-to-Target Trial, which showed that the addition of once-daily basal insulin glargine to oral agents, using a structured titration algorithm based on fasting plasma glucose monitoring, can achieve stringent glycemic control with less risk of nocturnal hypoglycemia than NPH insulin.