Macrophages have emerged at the forefront of research in immunology and transplantation because of recent advances in basic science. New findings have illuminated macrophage populations not identified previously, expanded upon traditional macrophage phenotypes, and overhauled macrophage ontogeny. These advances have major implications for the field of transplant immunology. Macrophages are known to prime adaptive immune responses, perpetuate T-cell–mediated rejection and antibody-mediated rejection, and promote allograft fibrosis. In this review, macrophage phenotypes and their role in allograft injury of solid organ transplants will be discussed with an emphasis on kidney transplantation. Additionally, consideration will be given to the prospect of manipulating macrophage phenotypes as cell-based therapy. Innate immunity and macrophages represent important players in allograft injury and a promising target to improve transplant outcomes.