(Macro-)autophagy is an evolutionary conserved 'self-digestion program' that serves to maintain cellular metabolism and is implicated in many pathological processes such as cancer. In recent years, an increasing number of studies in murine cancer models have provided a plethora of sometimes conflicting results about the role of autophagy in cancer biology. This review summarizes these studies and raises awareness that there are situations in which autophagy blockage might indeed reduce tumor growth, but that sometimes the exact opposite is the case. It is therefore vital to mimic patient conditions in preclinical mouse experiments as thoroughly as possible before commencing clinical trials.