Structural and functional diversity of cellular types is mainly the result of combinatorial regulation of gene expression in which transcriptional factors interact in different ways and different combinations in response to signaling pathways. MADS-box transcription factors are found in all eukaryotic kingdoms and they are of key importance in signal transduction to the genome. MADS-box factors interact with other regulatory proteins in complexes which can activate or repress transcription. In many cases these additional proteins influence the affinity and specificity of the complex for the target sequence. They can change the chromatin structure and decide which group of genes is regulated in a specific way. The MADS domain is a distinctive feature of the MADS-box transcription factors. It is a highly conserved domain of approximately 80 amino acids, responsible for DNA binding and bending, dimerization and interactions with other proteins. In animal cells MADS-box transcription factors participate in regulation of cell growth and differentiation, embryogenesis and morphogenesis. In yeast they are involved in the control of cell cycle progression, regulation of mating type specific genes, control of arginine metabolism, cell wall biosynthesis and osmotic stress response. Plant MADS-box proteins provide different homeotic functions determining floral organ development. This review is aimed at characterizing how MADS-box transcription factors interact with other regulatory proteins and how they are activated by different signal transduction pathways. We also summarize recent theories concerning the evolution of this family of transcriptional regulators.