Patients with noninsulin-dependent diabetes mellitus (NIDDM) are characterized by a loss of the normal ability of insulin to stimulate glucose uptake. The effects of diet, exercise, sulfonylurea compounds, and exogenous insulin on in vivo insulin-stimulated glucose uptake have been reviewed in this presentation. Although there is still a great deal to learn about the manner in which these various forms of treatment affect in vivo insulin action, the available information provides a rational framework for therapeutic attempts to enhance insulin sensitivity in patients with NIDDM.