Insulin lispro is a recombinant insulin analog with transposed amino acids (proline and lysine) at positions 28 and 29 near the C-terminus of the B-chain. The most prominent practical advantage of insulin lispro over human soluble insulin lies in its very rapid onset of action. This property allows it to be injected immediately before meals and minimizes the demands made on patients with type 1 diabetes mellitus, and those with type 2 disease who require insulin, by the ongoing need for careful meal planning and timing. Numerous clinical studies have shown significant improvements in postprandial glycemic control, with some evidence of reduced rates of severe or nocturnal hypoglycemia, relative to conventional human insulin in patients receiving lispro-based insulins.Quality-of-life studies show consistent preferences by patients for and increased treatment satisfaction with insulin lispro over human soluble insulin, particularly with variations of the Diabetes Treatment Satisfaction Questionnaire. Willingness of patients and taxpayers to pay additional costs for insulin lispro or a premixed lispro-based formulation over conventional human insulins, and cost benefits favoring formulary inclusion, have been shown in well designed studies carried out in Australia and Canada. Spanish data suggest cost effectiveness in terms of episodes of severe hypoglycemia avoided, and preliminary German resource utilization data indicate cost savings related to reduced hospitalization and general practice costs, with insulin lispro relative to human soluble insulin.Conclusions: Insulin lispro and premixed formulations of lispro-based insulins offer quality-of-life improvements relative to conventional human insulins in patients with diabetes mellitus. Participants in well designed studies have expressed a preference for lispro-based insulins and have been shown to be willing to pay for the advantages they offer, and current cost-benefit data favor the inclusion of these insulins in formularies and their reimbursement by third party payers. Further research into the pharmacoeconomic implications of insulin lispro use in the long term is needed, particularly with respect to effects on indirect costs and those associated with complications of diabetes mellitus.