Stat5 is constitutively activated in many human cancers affecting the expression of cell proliferation and cell survival controlling genes. These oncogenic functions of Stat5 have been elegantly reproduced in mouse models. Aberrant Stat5 activity induces also mitochondrial dysfunction and reactive oxygen species leading to DNA damage. Although DNA damage can stimulate tumorigenesis, it can also prevent it. Stat5 can inhibit tumor progression like in the liver and it is a tumor suppressor in fibroblasts. Stat5 proteins are able to regulate cell differentiation and senescence activating the tumor suppressors SOCS1, p53 and PML. Understanding the context dependent regulation of tumorigenesis through Stat5 function will be central to understand proliferation, survival, differentiation or senescence of cancer cells.