Dendritic cells and macrophages are critical early initiators of innate immunity in the kidney and orchestrate inflammation subsequent to ischemia-reperfusion injury. They are the most abundant leukocytes present in the kidney, and they represent a heterogeneous population of cells that are capable of inducing sterile inflammation after reperfusion directly through the production of proinflammatory cytokines and other soluble inflammatory mediators or indirectly through activation of effector T lymphocytes and natural killer T cells. In addition, recent studies have indicated that kidney and immune cell micro-RNAs control gene expression and have the ability to regulate the initial inflammatory response to injury. Although dendritic cells and macrophages contribute to both innate and adaptive immunity and to injury and repair, this review focuses on the initial innate response to kidney ischemia-reperfusion injury.