c-Myc is frequently deregulated in human cancers. The c-Myc oncoprotein is a transcription factor, with many of its target genes encoding proteins that initiate and maintain the transformed state. c-Myc is also part of a dynamic network whose members interact selectively with one another and with various transcriptional coregulators and histone-modifying enzymes. This knowledge highlights several points that might be amenable to attack. This review summarizes progress in controlling the extent of c-Myc transcription, translation, interaction with other myc network members, DNA binding and transcriptional activation. Inhibition of c-Myc can be achieved with many of these approaches; however, clinical efficacy will likely require intervention at several levels, perhaps in combination with traditional chemotherapeutic drugs or agents that target other oncoproteins.