Hyperglycemia occurs frequently in critically ill patients, including patients with previously known or unrecognized type 1 or type 2 diabetes mellitus (DM), or in those with previous normoglycemia (stress hyperglycemia). Stress hyperglycemia refers to a transient increase in blood glucose (BG) concentration during acute illness in patients with no previous history of diabetes. Several studies in critically ill patients have demonstrated a positive correlation between stress hyperglycemia and poor clinical outcomes, such as longer hospital stay and increased morbidity and mortality. Insulin therapy is the mainstay of diabetes control in setting of cardiodiabetes with other comorbidities. It helps us in appropriate glycemic control, thereby improves fast recovery. Guidelines of insulin therapy in critical care, recommendations, and insulin infusion protocols are also covered in this chapter.