Antibodies that block CTLA-4 (cytotoxic T lymphocyte–associated antigen 4) and PD-1 (programmed death 1) allow T cells to launch antitumor immune responses. Although these checkpoint inhibitors improve survival in melanoma patients, inflammation of other tissues is a common side effect. Johnson et al. report that two melanoma patients treated with a combination of the checkpoint inhibitors developed fatal cardiac damage. Biopsies revealed that T cells and macrophages that infiltrated the heart were the same as those found in skeletal muscle and the tumor. Neither patient had cardiac risk factors other than hypertension. Review of a safety database suggests that severe myocarditis from such combination therapy affects less than 1% of patients. The mechanism for this rare toxic effect is not known.