This perspective was written in celebration of Dr Arnold J. Levine’s 80th birthday. I chose to write this prospective about restoration of p53 activity in tumors for two reasons: Arnie (as we all know him) has become interested in restoring p53 activity in tumor cells and such a review did not exist. Arnie was also my postdoctoral advisor and writing this perspective is just a small tribute for the huge impact he has had on my research career (and that of many others), from supporting me when I left his laboratory for a faculty position before I had even published a paper, to serving as a sounding board for numerous ideas. Arnie is an amazing thinker. He is able to almost effortlessly incorporate new knowledge into current thinking and collate a big picture. It has been my pleasure to interact with him scientifically on numerous occasions. I want to thank Arnie from the bottom of my heart for sharing with me his love of science, his critical thinking skills, and his friendship