The concept of chimeric antigen receptor (CAR) was pioneered in 1989 by Eshhar and colleagues with the specific goal of providing an alternative means by which T lymphocytes can engage antigens expressed by target cells.1 Until recently, the focus of CAR–T cell research has been on achieving effector function in T lymphocytes that can target cancer cells and destroy them. In this issue of Molecular Therapy, however, Eshhar's group illuminates another face of CAR-based technology.2 They engrafted CARs in naturally occurring regulatory T cells (nTregs) to produce “loss of function” of an unwanted T-cell response that causes inflammation, thereby ameliorating an ongoing autoimmune disorder (Figure 1).