Genetically engineered T cells are powerful new medicines, offering hope for curative responses in patients with cancer. Chimeric antigen receptor (CAR) T cells were recently approved by the US Food and Drug Administration and are poised to enter the practice of medicine for leukemia and lymphoma, demonstrating that engineered immune cells can serve as a powerful new class of cancer therapeutics. The emergence of synthetic biology approaches for cellular engineering provides a broadly expanded set of tools for programming immune cells for enhanced function. Advances in T cell engineering, genetic editing, the selection of optimal lymphocytes, and cell manufacturing have the potential to broaden T cell–based therapies and foster new applications beyond oncology, in infectious diseases, organ transplantation, and autoimmunity.