Until recently, basophils and mast cells were considered mainly effector cells with an innate immune response linked to allergy and parasite infection. Only in the past few years they were recognized as important regulators of adaptive immunity. The development of new methods and reagents has enabled detection and functional analysis of these rare cells in patients and murine disease models. Basophils are normally present in the peripheral blood, spleen, and bone marrow, but migrate into lymph nodes and tissues during inflammation. They are rapidly activated by cytokines (e.g., interleukin (IL)-3) and intact antigens that cross-link surface-bound immunoglobulins. Activated basophils change the phenotype of T cells toward Th2 and markedly support humoral memory responses. Mast cells also migrate into lymph nodes and interact with dendritic cells, T cells, and B cells. In this review, we describe how mast cells and basophils affect immune responses and discuss implications for renal diseases and transplant rejection.