Cell and molecular biological studies of p53 functions over the past 30 years have been complemented in the past 20 years by studies that use genetically engineered mice. As expected, mice that have mutant Trp53 alleles usually develop cancers of various types more rapidly than their counterparts that have wild-type Trp53 genes. These mouse studies have been instrumental in providing important new insights into p53 tumour suppressor function. Such studies have been facilitated by the development of increasingly sophisticated genetic engineering approaches, which allow the more precise manipulation of p53 structure and function in a mammalian model.