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Understanding when to use insulin and how to apply the principles of physiologic insulin replacement using existing and new insulins is a key step to improving diabetes care. Insulin analogues and premixed insulins increase physicians' and patients' ability to lower hemoglobin A 1C levels with fewer episodes of hypoglycemia. Earlier use of insulin and more aggressive dose escalation are important steps in achieving treatment goals. This article discusses using bedtime insulin with oral agents, basal-prandial insulin strategies, and the new insulin analogues.