In all organisms, correct development, growth and function depends on the precise and integrated control of the expression of their genes. Often, gene regulation depends upon the cooperative binding of proteins to DNA and upon protein-protein interactions. Eukaryotes have widely exploited combinatorial strategies to create gene regulatory networks. MADS box proteins constitute the perfect example of cellular coordinators. These proteins belong to a large family of transcription factors present in most eukaryotic organisms and are involved in diverse and important biological functions. MADS box proteins are combinatorial transcription factors in that they often derive their regulatory specificity from other DNA binding or accessory factors. This review is aimed at analyzing how MADS box proteins combine with a variety of cofactors to achieve functional diversity.