CD45, an abundant and highly glycosylated cell‐surface protein, is a critical regulator of T‐cell development. CD45 is differentially glycosylated throughout the life of a T cell, and the glycosylation state of CD45 controls recognition by various binding partners, affects intracellular signaling by the cytoplasmic tyrosine phosphatase domain and modulates the response of the T cell to antigen. Although the importance of CD45 during T‐cell development has been established, it is becoming increasingly clear that glycosylation of CD45 is a dynamic process that modifies T‐cell survival, activation and immune function. In this review, we address changes that occur in CD45 glycosylation during T‐cell development and differentiation, describe carbohydrate‐binding proteins that recognize differentially glycosylated forms of CD45, and discuss how differential glycosylation alters the T‐cell response to a variety of signals involved in selection, activation and apoptosis.