Abstract Emerging evidence suggests that the proapoptotic kinase mammalian sterile 20–like kinase 2 (MST2) acts in a novel tumor suppression pathway. Recently, we showed that Raf-1 kinase sequesters and inhibits MST2 and that this event is critical for Raf-mediated cell survival. In this review, we summarize Raf control of MST2 and we outline a novel pathway involving the downstream effector proteins Salvador and Warts/Lats that may act to limit the positive effects of Raf–mitogen-activated protein kinase signaling in cancer cells.