Survival rates of patients with metastatic or recurrent cancers have remained virtually unchanged during the past 30 years. This fact makes the need for new therapeutic options even more urgent. An attractive option would be to target autophagy, an essential quality control process that degrades toxic aggregates, damaged organelles, and signaling proteins, and acts as a tumor suppressor pathway of tumor initiation. Conversely, other fascinating observations suggest that autophagy supports cancer progression, relapse, metastasis, dormancy and resistance to therapy. This review provides an overview of the contradictory roles that autophagy plays in cancer initiation and progression and discusses the promises and challenges of current strategies that target autophagy for cancer therapy.