In normal humans, blood glucose and insulin are maintained within a narrow range despite wide variations in physical activity and dietary intake. At present, reproducing this pattern is an impossible task in type 1 diabetes and extremely difficult in type 2 DM. New approaches using novel insulin analogs and routes of administration, attempting to replicate physiological insulin secretion in diabetic patients, are improving the profiles of glucose levels and, thus, the quality of life. Ultra-short-acting insulin analogues and ultra-long-acting analogues are being used for prandial and basal effects with better results, lower prevalence of hypoglycemia, and, hopefully, fewer chronic complications. Non-invasive routes of administration are being developed. The most promising appears to be inhaled insulin according to studies demonstrating excellent control, apparently without significant side effects, although in relatively short-term trials. Longer-term studies to assure the safety are still necessary before recommending its extended use. This is an extensive, up-to-date review of recent advances in insulin therapy.