Renal disease results from a variety of insults, but whatever its genesis, ongoing inflammation will drive progressive fibrotic disease. Dendritic cells link innate and adaptive immunity by presenting antigens, but they act also in an antigen-independent manner. While systemic dendritic cells (DCs) establish nephritogenic adaptive immunity, DCs are also present in the kidney. The tubulointerstitium is endowed with a network of mononuclear phagocytes, many having dendritic cell characteristics. While the roles of renal DCs are complex, recent evidence demonstrates that in adaptive immune responses affecting the kidney, DCs in the cortical interstitium express the chemokine receptor CX3CR1, are CX3CR1 dependent and are important in ongoing antigen recognition by effector CD4+ T cells, leading to progressive disease. Medullary DCs do not share this potent antigen-presenting function and CX3CR1 dependence. Though macrophages have a pathogenic role in antigen-independent renal fibrosis, whether interstitial DCs have any role is not clear. The participation of local and systemic DCs in progressive renal disease varies according to their involvement as antigen-presenting or local innate cells, the nature of the pathogenic process, and the involvement of the glomerulus, the cortical tubulointerstitium and the medulla in disease.