The immunological synapse (IS) formed between immune cells and antigen-presenting cells (APCs) provides a platform for signaling. Protein kinase C (PKC)θ localizes in the T cell IS within the central supramolecular activation cluster (cSMAC), where it associates with CD28 and mediates T cell receptor (TCR)/CD28 signals leading to effector T (Teff) cell activation. In regulatory T (Treg) cells, PKCθ is sequestered away from the IS, and inhibits suppressive function. Other PKCs localizing in the IS mediate additional functions in various immune cells. Further work is needed to identify mechanisms underlying PKC recruitment or exclusion at the IS, potential redundancy among IS-localized PKCs, and the relevance of PKC localization for IS dynamics and lymphocyte activation.