New-onset diabetes mellitus after transplantation is characterized by decreased insulin secretion and increased insulin resistance secondary to the effects of immunosuppression. Although impaired P cell function appears to be the primary mechanism of calcineurin inhibitor-induced new-onset diabetes, impaired peripheral glucose utilization also appears to contribute to insulin resistance and abnormal glucose metabolism. Because transplant recipients who develop new-onset diabetes mellitus after transplantation are at increased risk for infections, cardiovascular disease, and poor patient and graft survival, all patients should undergo careful assessment of risk for diabetes prior to transplantation and regular screening for the development of hyperglycemia thereafter. For patients in high-risk groups, including certain ethnic backgrounds, older adults, and the very young, and patients with hepatitis C, consideration should be given to initiating immunosuppressive therapy with agents that are less diabetogenic. Recent guidelines include more stringent criteria for diagnosis and stress the importance of strict glycemic control. Diet, exercise, and weight management are core components of treatment with addition of oral hypoglycemic agents and/or insulin as needed to achieve control. Concomitant measures include aggressive control of lipids and blood pressure to reduce the risk of cardiovascular disease. New-onset diabetes after transplantation is a serious issue affecting patient and graft outcomes and warrants the attention of all health care professionals involved in assessing and managing the transplant recipient.