Autophagy describes several metabolic pathways, by which cytoplasmic constituents are imported into lysosomes for degradation. These pathways and in particular macroautophagy play an important role during oncogenesis by apparently inhibiting cellular transformation initially, but then ensuring tumor cell survival in established cancers. Furthermore, the conditioning of the tumor microenvironment, including the cross-talk with the immune system, is influenced by autophagy. These multiple facets of autophagy regulation in tumors will be discussed in the series of review articles of this issue of Seminars in Cancer Biology. A comprehensive understanding of this pathway in oncology is needed to efficiently apply autophagy regulating tumor therapies, which are already in use.