The murine double minute 2 (Mdm2) is a critical negative regulator of the p53 tumor suppressor. Almost 10 years ago, a search for new p53-interactors revealed the existence of an Mdm2-structurally related protein, Mdmx (or Mdm4). Since then a large body of biochemical data has accumulated on the functions of Mdmx, often leading to conflicting molecular models. Nevertheless, virtually all these data pointed toward a critical role for Mdmx in the regulation of the p53-Mdm2 network. A view that was recently confirmed by genetic studies. This review is a summary of our current understanding of this molecule, its structure and biological functions, as well as its relationship to its known binding partners. © 2005 Elsevier Inc. All rights reserved.