Protein arginine methylation has emerged as a key regulator of signal transduction with an important role in T lymphocyte activation. The predominant methyl transferase PRMT-1 is highly expressed in T helper cells, and ligation of the T cell antigen and costimulatory receptors, induces arginine methylation on several cytoplasmic proteins. Global inhibition of methyl transferases can result in signaling defects in CD4 T cells and profound immunosuppression. Here we suggest that manipulating protein arginine methylation could be a feasible strategy to modulate T lymphocyte function, presenting a novel approach towards immunotherapy and the treatment of T cell-mediated disorders such as autoimmune disease and transplant rejection.