The differentiation of lymphocyte subsets plays an important role in transplant medicine. The review describes alterations in the expression of surface molecules on circulating T cells associated with immunosuppressive therapy. Phenotypic changes are reflecting the various stages of T cell development, the degree of thymic involution, and disease- and treatment-associated perturbations. The most pronounced effects on T cell subsets are mediated by depleting therapies with mono- or polyclonal antibodies. The lymphopenia-induced homeostasis-driven proliferation leads to a novel homeostasis characterized by the expansion of cell subsets that characteristically show a phenotype of terminally differentiated cells such as CD8+CD57+CD28- T cells. Cells with these markers have long been linked with suppressor functions and recent data suggest their specific regulatory role. In addition cell phenotypes seen in transplant patients show striking similarities with changes in immune cells associated with aging. These phenotypic changes suggest an accelerated aging of the immune system in transplantation.