Cellular senescence is an irreversible cell cycle arrest that curbs unrestrained, aberrant proliferation of mammalian cells and is now recognized as a prominent tumor suppressive mechanism. We have shown recently that the E3 SUMO ligase PIASy actively contributes to execution of the senescence program, thus, providing the first evidence for a direct role of SUMO modification in this process. Here, we discuss some of the implications for this novel connection and future directions to study in more detail the importance of the SUMO pathway in senescence and tumorigenesis.