N-myc (MYCN), a member of the Myc family of basic-helix-loop-helix-zipper (bHLHZ) transcription factors, is a central regulator of many vital cellular processes. As such, N-myc is well recognized for its classic oncogenic activity and association with human neuroblastoma. Amplification and overexpression of N-myc has been described in other tumor types, particularly those of neural origin and neuroendocrine tumors. This review outlines N-myc's contribution to normal development and oncogenic progression. In addition, it highlights relevant transcriptional targets and mechanisms of regulation. Finally, the clinical implications of N-Myc as a biomarker and potential as a target using novel therapeutic approaches are discussed.