Autophagy serves a dichotomous role in cancer and recent advances have helped delineate the appropriate settings where inhibiting or promoting autophagy may confer therapeutic efficacy in patients. Our evolving understanding of the molecular machinery responsible for the tightly controlled regulation of this homeostatic mechanism has begun to bear fruit in the way of autophagy-oriented clinical trials and promising lead compounds to modulate autophagy for therapeutic benefit. In this manuscript we review the recent preclinical and clinical therapeutic strategies that involve autophagy modulation in cancer.