Non-apoptotic forms of programmed cell death are targets for novel approaches in anticancer therapy. Indeed, cancer cells often present with mutations in the apoptotic machinery that result in resistance to most anticancer therapies and contribute to a relatively low response rate to therapies based on the use of pro-apoptotic strategies. (Macro-)autophagy can be a highly efficient mode of cell death induction by excessive self-digestion as demonstrated by our experiments that studied the effect of radiation to induce autophagy cell death in apoptosis-deficient cells. Despite current controversies on the possible role of autophagy in the process of carcinogenesis and cancer progression by promoting cell survival, autophagy can be seen as a backup cell death mechanism, when other cell death mechanisms fail. This review will focus on the pathways linking autophagy and cancer that are relevant for target identification and on pharmaceuticals that can be utilized to improve cancer therapy by targeting the autophagic pathway. © 2007 Elsevier Ltd. All rights reserved.