The basic helix–loop–helix protein Myc is a renowned transcription factor controlling disparate aspects of cell physiology that, together, allow efficient proliferation of somatic cells. This ability, together with the observation that its deregulated expression occurs in the majority of human cancers, suggests that Myc could be a good therapeutic target. However, several aspects of Myc biology remain elusive: what is the major difference between oncogenic and physiological Myc? How does oncogenic Myc evade the intrinsic tumor surveillance pathways provided by evolution? If Myc inhibition were even possible, what would be the consequences for the homeostasis of normal proliferating tissues versus the fate of cancer cells? Here we summarize the latest works addressing these issues.