Patients with poorly controlled diabetes mellitus have a number of abnormalities in polymorphonuclear leukocyte (PMN) function and metabolism that are reversible with insulin treatment. Since host defense mechanisms in general have a great deal of reserve capacity, these defects alone do not appear to predispose diabetics to infection. However, when neuropathy and, particularly, arterial vascular disease are present, certain life-threatening microbial infections, almost unique to diabetes, may involve soft tissues and fasciae of the lower extremities, the external auditory canal, gall bladder, and sinuses. Even though the involved sites are anatomically diverse, all of these uncommon infections are associated with tissue ischemia and necrosis and require prompt surgical debridement and antimicrobial therapy. A second common infection in diabetes is candidiasis. Hyperglycemia contributes to the high frequency ofCandidainfection in two ways: 1) by glycosylating the active site on complement (C3), inhibiting the opsonization of bacteria; and 2) by inducing the production of a protein inCandidathat is structurally and functionally homologous to the PMN complement receptor, thus interrupting the normal complement-PMN interaction. These two mechanisms likely contribute to the persistence ofCandidainfections in poorly controlled diabetic patients. Since these abnormalities are reversible, improved glycemic control is essential for the successful treatment of this common yeast infection. In light of the fact that the serious life-threatening infections in diabetes are associated with underlying macro and microvascular disease, their elimination would appear to ultimately depend on our success in preventing the arterial vascular complications of diabetes.