The loss of p53 function is a very important event in cancer. The absence of a functional p53 in tumours favours cancer development, and it has been suggested that it also influences the efficacy of both chemotherapy and radiotherapy. The p53 pathway is therefore the subject of intense research, both in academia and in industry, to identify new compounds targeting tumours with an altered p53. Different strategies are currently under investigation. They can be divided into two groups: biological and chemical strategies. The biological strategies utilise the immune system to eliminate the tumours overexpressing p53 mutants. Alternatively they use vectors delivering a functional p53 gene in tumours or engineered viruses, which selectively target p53-defective cells. The chemical strategies are based on the design of compounds that stabilise or activate the p53 mutant proteins, inhibit the interaction between p53 and hdm2, or act on the p53-binding chaperone proteins. In this review, the current progress in these different approaches will be analysed.