Throughout 2008, we will publish a series of specially commissioned articles that discuss the key issues and our current knowledge of MYC and cancer. Since the isolation of the MYC oncogene in the early 1980’s, the concepts that try to explain how this transcription factor contributes to tumorigenesis are numerous and encompass many fields. And yet, new ideas about MYC–dependent responses and how these might be involved in tumorigenesis are still emerging as the repertoire of signalling pathways that are induced downstream of MYC activation expand. In addition, key concepts implicit in the consideration of how MYC might function as an oncogene are also likely to be relevant to other oncogenes and transcription factors, and may have therapeutic relevance.