Advances in understanding mast cell biology reveal their diverse functional capacity well beyond already established roles in host defense against parasites and allergic disease. Mast cells can initiate, amplify, and direct innate and adaptive immune responses. They also modulate inflammation and regulate immunity. Mast cells potentially induce tissue repair and direct fibrosis; however, they also play other roles in tissue remodeling and repair. Various activation and differentiating signals result in a diverse range of functional phenotypes called "mast cell heterogeneity." Mast cells are significant participants in chronic progressive kidney disease, and their presence is associated with function loss and fibrosis. This suggests a potential role in the fibrotic process, which may involve mast cell activation of local renin-angiotensin systems. Experimental animal studies suggest, however, they do not directly cause renal fibrosis but rather spark inflammation. Evidence for both pro- and anti-inflammatory roles in nephritis is emerging.