PTEN is a tumor suppressor best characterized for its role as a lipid phosphatase in antagonizing the PI3-kinase pathway. Several recent studies have identified proteins that form high molecular weight complexes with PTEN in different subcellular compartments. PTEN is critical for early embryonic development, cell proliferation, cell survival and stem cell function. The discovery of PTEN complex components may help our understanding of its biological functions. In this review, PTEN complex components, functions and their regulation will be discussed.