Autophagy is a progressive conserved catabolic mechanism, by which eukaryotic cells recycle or degrades internal constituents through the membrane-trafficking pathway. Thus, autophagy provides the cells with a sustainable source of biomolecules and energy for the maintenance of homeostasis under stressful conditions such as tumor microenvironment.It is generally believed that modulating autophagic activity, through targeting specific regulatory actors in the core autophagy machinery, may impact disease processes. Both autophagy upregulation and down regulation have been found in cancers, suggesting its dual oncogenic and tumor suppressor properties during malignant transformation. Identification of the key autophagy targets is essential for the development of new therapeutic agents. In this review the two-faced role of autophagy in cancer as a tumor suppressor or as a pro-oncogenic mechanism discussed and the shared regulatory pathways that play a role in autophagy and malignant transformationillustrated. Finally, anti-cancer therapeutic agents used as either inhibitors or inducers of autophagy have been discussed.