Hyperglycemia in patients with and without known diabetes is a common finding in patients hospitalized with cardiovascular disease, and is associated with poor outcomes. Investigators have been examining the role of insulin to treat patients with acute myocardial infarction since the 1960's. Until the 1990's most studies evaluated fixed doses of glucose-insulin-potassium (GIK) infusions. The Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) trial, published in 1995, evaluated the role of adjustable-dose insulin infusion to lower blood glucose. Its promising results spurred further interest and a number of trials evaluating the use of insulin to lower blood glucose in hospitalized patients - many of which included patients with cardiovascular disease - have been conducted over the last two decades with conflicting results. This manuscript reviews the epidemiology and pathophysiology of hyperglycemia in hospitalized patients, summarizes the evidence for benefits and harms of using insulin to treat hyperglycemic patients hospitalized with cardiovascular disease, and offers some practical management considerations.