This edition of the Med-Psych Drug-Drug Interactions Update begins a change in format. Starting with this column, each column will feature one drug-drug interaction (DDI) topic that will be explored in depth. This edition features DDIs associated with the commonly used immunosuppressants. These drugs are frequently encountered by consultation-liaison psychiatrists in tertiary care settings. Generally, most of these drugs have narrow safety and therapeutic windows; therefore, other drugs that change their serum levels can have deleterious effects. In this review, the DDI profiles of cyclosporine, tacrolimus, sirolimus, and the corticosteroids are explored.