The phosphoinositide 3-kinase signaling pathway has been implicated in a range of T lymphocyte cellular functions, particularly growth, proliferation, cytokine secretion, and survival. Dysregulation of phosphoinositide 3-kinase-dependent signaling and function in leukocytes, including B and T lymphocytes, has been implicated in many inflammatory and autoimmune diseases. As befits a pivotal signaling cascade, several mechanisms exist to ensure that the pathway is tightly regulated. This minireview focuses on two lipid phosphatases, viz. the 3'-phosphatase PTEN ( phosphatase and tensin homolog deleted on chromosome 10) and SHIP ((S) under bar rc (h) under bar omology 2domain-(c) under bar ontaining (i) under bar nositol-5-(p) under bar hosphatase). We discuss their role in regulating T lymphocyte signaling as well their potential as future therapeutic targets.