The p53 protein is one of the most important tumor suppressors. The present review summarizes aspects of p53 function and its role in cancer development. Some of the most well-characterized molecular mechanisms affecting p53 regulation, stabilization, inactivation and downstream events are described. A major focus is on how xenobiotics can interfere with p53 function and on its role in chemical carcinogenesis. In the final section of this chapter we discuss future aspects on how knowledge about p53 can be used in testing of carcinogens and in risk assessment.