Myc expression is deregulated in a wide range of human cancers and is often associated with aggressive, poorly differentiated tumors. The Myc protein is a transcription factor that regulates a variety of cellular processes including cell growth and proliferation, cell-cycle progression, transcription, differentiation, apoptosis, and cell motility. Potential strategies that either inhibit the growth promoting effect of Myc and/or activate its pro-apoptotic function are presently being explored. In this review, we give an overview of Myc activation in human tumors and discuss current strategies aimed at targeting Myc for cancer treatment. Such therapies could have potential in combination with mechanistically different cytotoxic drugs to combat and eradicate tumors cells.