This paper describes the biological functions of PTEN and the PTEN regulated signaling pathway in pancreatic β-cells. PTEN has been shown to regulate the regeneration of β-cells. We review the pathways that are controlled by PTEN signaling and their functions in β-cell regeneration. In particular, we describe the unique effect of Pten deletion in β-cells. Unlike its effect in other tissues, Pten deletion does not lead to tumor formation but does enhance β-cell proliferation and function. In addition to the literature review, we also report new results exploring PTEN loss in adult β- cells. We demonstrate that inducing PTEN loss in adult cells has the same regenerative effects previously found for prenatal deletion.