Macroautophagy (referred to as autophagy in this review) is a genetically regulated bulk degradation program conserved from yeast to humans, in which cytoplasmic substrates, such as damaged organelles and long-lived proteins, are delivered to lysosomes for degradation. In this review, we consider recent data that highlight possible mechanisms whereby autophagy mediates cytoprotective effects. These include the ability of autophagy to buffer against starvation, protect against apoptotic insults and clear mitochondria, aggregate-prone proteins and pathogens. These effects are pertinent to the roles of autophagy in normal human physiology, including the early neonatal period and ageing, as well as a variety of diseases, including cancer, neurodegenerative conditions and infectious diseases.