The human homologue of the mouse double minute 2 (MDM2) oncogene is overexpressed in more than forty different types of malignancies, including solid tumors, sarcomas and leukemias. Because of its prevalent expression and its interactions with p53 and other signaling molecules, MDM2 plays a central role in cancer development and progression. The expression of this oncoprotein is being studied by researchers world-wide, and the amount of data published about it is increasing exponentially. Although there are some conflicting data about the effects of MDM2 expression in individual cancers, the overall evidence is convincing, indicating that increased MDM2 expression is related to a worse clinical prognosis. There is an increased likelihood of distant metastases, as well as a decreased response to therapeutic intervention in MDM2-positive cancers. MDM2 may also serve as a diagnostic marker, not only for cancer stage, but to differentiate between similar cancers. MDM2 may also be associated with drug resistance in cancer chemotherapy. These findings make studying the oncoprotein necessary to aid in our understanding of cancer development, to identify novel cancer drug targets, and to increase the efficacy of cancer therapy.