The autophagosome is the central organelle in macroautophagy, a vacuolar lysosomal catabolic pathway that degrades cytoplasmic material to fuel starving cells and eliminates intracellular pathogens. Macroautophagy has important physiological roles during development, ageing and the immune response, and its cytoprotective function is compromised in various diseases. A set of autophagy-related (ATG) proteins is hierarchically recruited to the phagophore, the initial membrane template in the construction of the autophagosome. However, recent findings suggest that macroautophagy can also occur in the absence of some of these key autophagy proteins, through the unconventional biogenesis of canonical autophagosomes. Such alternatives to the evolutionarily conserved scheme might provide additional therapeutic opportunities.