Orlistat, a pancreatic lipase inhibitor, was approved by the US Food and Drug Administration (FDA) in the spring of 1999 as an adjunct to lifestyle intervention for weight loss. This paper seeks to examine current issues regarding orlistat use in patients with type 2 diabetes. There are a number of trials that demonstrate the benefits of orlistat over placebo for reducing body weight and improving other health parameters. Of some interest are the preliminary explorations of interaction on cytokine levels, where a possible cardiovascular benefit is plausible. Implications of the FDA approval of over-the-counter use and the pharmaceutical development of another lipase inhibitor are also examined.