Chimeric antigen receptor (CAR) T and natural killer (NK) cell therapies represent a promising strategy for the treatment of cancers and other chronic diseases. Engineered CAR constructs endow immune cells with the ability to target desired antigens with high specificity, allowing for directed responses to antigen-expressing cells. CAR T and NK cells have shown marked success in the treatment of hematologic malignancies, although there remains a large population of patients with disease that fails to respond to CAR therapies, and their efficacy in solid tumors is still limited. In this review, we provide a broad overview of the development, design, and implementation of CAR therapies from bench to bedside. We discuss the building blocks of CAR constructs and how these can be manipulated to optimize CAR functionality, review the possible sources of T and NK cells for CAR therapies, and examine the limitations of both CAR T and CAR NK cells. Finally, we discuss recent breakthroughs in the CAR field and consider how these advances may affect the success of CAR therapies in the years to come.