Clinicians are frequently required to manage situations for which few data are available in the literature. Medical therapies for these situations are frequently based on graduate and postgraduate training, community standards, and personal experience. For individuals with diabetes, this would include perioperative diabetes management, the management of diabetes while discontinuing an insulin infusion, and the management of diabetes during treatment with glucocorticoids and TPN. Clinicians may disagree with some of the recommendations for these four situations, and implementation of these suggestions may not be possible at all hospitals. The therapies described herein are based on the pathophysiology of the respective situation and the pharmacokinetic and pharmacodynamic properties of available medications, particularly insulin. The introduction of new insulin analogues and agents to treat insulin resistance may improve our ability to treat diabetes in special situations. Future investigations should focus on how to best use these tools during critical times.