Myc proteins are nuclear proteins that exert their biological functions at least in part through the transcriptional regulation of large sets of target genes. Recent microarray analyses show that several percent of all genes may be directly regulated by Myc. A large body of data shows that Myc proteins both positively and negatively affect transcription. The basic mechanism underlying Myc's activation of transcription is well understood, but the mechanisms through which Myc negatively regulates or represses transcription are far less understood. In this chapter, we will review our current knowledge about this less-well-understood topic.