The majority of cells comprising the inflammatory infiltrates in kidney allografts undergoing acute and/or chronic rejection are typically T cells and monocyte/macrophages with B cells, plasma cells, and eosinophils accounting for <5%. In a significant minority of biopsies, B lineage cells (B cells and/or plasma cells) may be found more abundantly. Although plasma cell infiltrates tend to be more diffuse, B cells tend to aggregate into nodules that may mature into tertiary lymphoid organs. Given the ability to target B cells with anti-CD20 monoclonal antibodies and plasma cells with proteasome inhibitors and anti-CD38 monoclonal antibodies, it is increasingly important to determine the significance of such infiltrates. Both cell types are potential effectors of rejection, but both also have a tolerizing potential. B cell infiltrates have been associated with steroid resistance and reduced graft survival in some studies but not in others, and their presence should not prompt automatic depletional therapy. Plasma cell-rich infiltrates tend to occur later, may be associated with cell-mediated and/or antibody-mediated rejection, and portend an adverse outcome. Viral infection and malignancy must be ruled out. Randomized controlled trials are needed to determine the appropriateness of specific therapy when B cells and/or plasma cells are found. No strong therapeutic recommendations can be made at this time.