The Myc family proteins are potent oncogenes that can activate and repress a very large number of cellular target genes. The amino terminus of Myc contains a transactivation domain that can recruit a number of nuclear cofactors with diverse activities. Functional studies link transactivation to the ability of Myc to promote normal cell proliferation and for oncogenic transformation. The biochemical mechanism of Myc-mediated transactivation has revealed a wide range of effects on chromatin and basal transcription. This review summarizes recent advances in understanding the function of Myc as a transcriptional activator and the role of this activity in Myc biological activities.