Intensive insulin therapy (IIT) and combination therapy using sulfonylurea and insulin are two insulin regimens being used more frequently to improve glycemic control. For those patients with insulin-dependent diabetes, IIT or multiple daily injection therapy mimics normal pancreatic function by its timing of insulin delivery. The improvement in glycemic control carries with it the risk of a two- to threefold increase in episodes of hypoglycemia. For those with non-insulin-dependent diabetes, combination therapy attempts to provide a bridge between maximal dose oral hypoglycemic agents and aggressive insulin therapy. Although this therapy remains controversial, it has proved useful in select patient groups. This article discusses the rationale for IIT, and its implementation. Variables that affect IIT are discussed. The combination therapy section provides guidelines for patient selection and insulin protocols for evening insulin administration. The health care provider is familiarized with these alternative therapies and their successful applications.