The interplay between Mdm2 and p53 represents one of the better-known paradigms of the relationship between an oncogene and a tumor suppressor gene. The Mdm2 protein is a key regulator of cell growth and death and plays a pivotal role in the transformation of normal cells into tumor cells, the hallmark of an oncogene. The primary role of Mdm2 under nonstressed conditions is to target the degradation ofthe tumor suppressor protein p53. In response to stress, however, p53 is not affected by Mdm2 and functions as a transcription factor that induces the transcription of Mdm2 as well as of genes involved in growth control or apoptosis. The effect of Mdm2 on the regulation of cell growth and death depends on p53 but also on a growing number of p53-independent targets. This overview summarizes our current understanding of Mdm2 and p53 regulation, function, and interaction in normal and tumor states.