Management of type 1 and type 2 diabetes mellitus with intensive insulin therapy usually includes an intermediate- or long-acting basal component for between-meal and nocturnal glycemic control, together with preprandial bolus injections of a short-acting insulin for control of meal-stimulated increases in serum glucose levels. Although the ideal basal/bolus insulin combination has yet to be found, recent developments may provide safer and more effective options. Two new short-acting semisynthetic analogs--insulin lispro and insulin aspart--can be administered as preprandial bolus injections closer to mealtime than regular human insulin, thereby synchronizing insulin administration and food absorption. In clinical trials, postprandial increases in blood glucose levels were significantly less after treatment with insulin lispro or insulin aspart than with premeal regular insulin. Because of their short duration of action, a slightly greater basal insulin supply may be needed when insulin lispro or insulin aspart is used. Inhalation devices for aerosolized regular human insulin offer another alternative to premeal subcutaneous bolus injections. Inhaled insulin is absorbed more rapidly than subcutaneous regular insulin and may therefore be given closer to mealtime. For basal therapy, insulin glargine, a new long-acting analog, is absorbed more slowly after subcutaneous administration than are conventional neutral protamine Hagedorn (NPH) and ultralente insulin, and has a relatively flat metabolic effect. Clinical trials indicate that insulin glargine is at least as effective as NPH insulin and ultralente insulin, and is associated with a reduced risk of nocturnal hypoglycemia. Other long-acting analogs, such as fatty acid acylated insulins, have been tested in animal models and are being evaluated in clinical studies.