Organ transplant rejection occurs when the transplant recipient's immune system identifies the transplanted organ as foreign tissue and attacks it. It was previously thought that T cells, the immune cells that mediate rejection, must first be activated by molecules known as chemokines in order to migrate to the transplanted organ. In this issue of the Journal of Clinical Investigation, Fadi Lakkis and colleagues at the University of Pittsburgh used mice to demonstrate that chemokine stimulation of T cells is not required for migration. Instead, these cells must come into contact with immune-stimulating proteins (antigens) that are specifically expressed by the transplanted organ. In an accompanying commentary, Terry Strom discusses how these findings could have important implications for the design of novel anti-rejection therapeutics.