The dual specific phosphatase PTEN (Phosphatase and TENsin homolog deleted on chromosome 10) is one of the most extensively studied proteins of the last decade. It was the first phosphatase identified as a tumor suppressor and in sporadic cancers PTEN is one of the most frequently altered genes. Its deregulation is also implicated in several other diseases. In addition, PTEN is critically important during embryonic development and is implicated as a key player in maintaining normal stem cell function. Unraveling of the physiological regulation and function of PTEN will augment our understanding of tumorigenesis and ultimately lead to novel therapeutic options.