The tumor suppressor p53 is one of the most complex and widely studied genes in cancer biology. In spite of the vast on literature the transcriptional regulation of p53, aspects of its especially epigenetic regulation are not completely understood. This chapter presents a concise overview of p53-related epigenetic events involved in oncogenesis and tumor suppression. We limit the scope to epigenetic modifications of the p53 promoter per se as well as its well-established downstream targets. The indirect role of p53 affecting the epigenetic machinery of cancer cells via specific proteins and transcription factors is discussed. Current concepts of p53-related cancer epigenetics offer myriad avenues for cancer therapies. Challenges in the field are also discussed.