The p53 gene is a tumour suppressor gene frequently mutated in human cancers. Its product is a transcription factor that regulates the expression of various genes involved in cell cycle arrest and in apoptosis in response to different cellular stresses. The recent discovery of two p53 gene homologs, p73 and p63, has uncovered a family of transcription factors and widened the scenario of cell cycle control and apoptosis. p73 and p63 genes encode proteins showing significant structural and functional similarity to p53, although important differences are emerging. p73 and p63 have an additional domain in their carboxyl-terminal region with marked similarity to the structure of SAM (sterile alpha motif) domains, typical of proteins involved in development. Indeed, differently from p53, p63 and p73 seem to be involved in development and differentiation. Both p73 and p63, at least when overproduced, can activate some of the p53-responsive promoters and trigger growth arrest and apoptosis, although their an swers in response to DNA damage differ from those of p53. The challenge is now to understand similarities and differences between family members especially in terms of their functions, regulation and interactions. This review summarizes the present knowledge on the structural, functional and evolutionary features of the p53 gene family and focuses on the differences among the three members of the family.