Most malignant tumors disrupt the p53 signaling pathway in order to grow and survive. Although many genes in addition to p53 are mutated in tumors, recent studies by Ventura et al. (2007) and Xue et al. (2007) suggest that restoring p53 function alone is sufficient to cause regression of several different tumor types in mice and thus might represent a potent therapeutic strategy to treat certain human cancers. Martins et al. (2006) also demonstrate that restoration of p53 activity results in tumor regression but add the sobering caveat that tumors may be able to quickly generate resistance by finding other ways to disrupt the p53 pathway.