This review aims to summarize the major advances of the preceding year and to put them in to the context of current opinion on diabetes mellitus . Despite the advent of life-prolonging insulin for the treatment of diabetes, the appearance and p rogression of many of the disabling complications associated with this disease cannot b e prevented through the administration of insulin. Clinically, the onset and rate of progress ion of diabetic complications, including cataract, corneal epitheliopathy, microangiopathy, nephropathy, neuropathy, and retinopathy, appear to be dependent upon both the duration and t he severity of the diabetes. This review summarizes the specific pathogenic mechanisms of mi crovascular complications for which clinical therapies have been developed, including t he polyol pathway, advanced glycation end products, protein kinase c, vascular epithelium gro wth factor, and the superoxide pathway. The review further focuses on therapies for these targe ts that are currently available or are undergoing late-stage clinical trials.