Autophagy is an important cellular recycling process that degrades misfolded proteins and damaged organelles. In typical (“canonical”) autophagy, membranes derived from the endoplasmic reticulum surround damaged materials that need to be degraded, and the proteins Atg5 and Atg7 help form specialized digestion compartments (autophagosomes), but another type of autophagy, called alternative autophagy, was recently discovered. In alternative autophagy, the membranes that envelop the damaged materials are derived from the trans-Golgi membrane, and Atg5 and Atg7 do not participate in autophagosome formation. Alternative autophagy seems to be activated primarily under conditions of cell stress, and it plays roles in many diseases, such as heart disease, neurodegenerative disease, cancer, inflammatory bowel disease, and bacterial infection. For example, alternative autophagy helps eliminate dysfunctional mitochondria in oxygen-deprived heart cell and helps protect against harmful bacterial infections in inflammatory bowel disease. Research on alternative autophagy is still in its infancy, and many questions remain to be answered. Future studies on animals lacking specific alternative autophagy-related genes may help distinguish the mechanisms of this process and suggest potential therapeutic targets for disease treatment.