Immunologists have typically viewed alloreactivity schematically as a function of antigen presentation, expansion of alloreactive T and B cells within regional lymphoid tissues, and cellular infiltration and destruction of an allograft. Actual details of the steps between immune activation and accumulation of effector cells within a graft typically have not received much attention. However, just how cells ‘know’ to move to and migrate within a graft or not is proving to be of increasing interest, as the chemokine‐dependent mechanisms underlying leukocyte recruitment to a transplant are dissected. Experimentally, chemokine receptor targeting can prolong or induce permanent allograft survival, despite preservation of alloresponses within secondary lymphoid tissues, whereas current immunosuppressive protocols have only modest effects on chemokine production and leukocyte homing. Recent knowledge of the chemokine‐dependent nature of allograft rejection, acceptance, and tolerance induction are presented as a basis for understanding the rationale for preclinical trials of chemokine receptor‐targeted therapies currently underway in primate recipients of solid organ allografts.