Autophagy is a highly conserved process in which damaged proteins and organelles are sequestered in double-membrane autophagosomes and delivered to lysosomes for degradation and recycling. As an efficient response to cellular stress, autophagy is essential for the maintenance of cellular homeostasis. Defective autophagy is associated with a variety of diseases, including cancer. This article summarizes current knowledge about the molecular mechanism of autophagy and its role in tumorigenesis. Particular focus is placed on the development of small-molecule regulators of autophagy and their potential application as anticancer therapeutic agents.