Autophagy (from the Greek auto – self, phagein – to eat), is the basic cellular catabolic mechanism that involves cell degradation of unnecessary or dysfunctional cellular components through the actions of lysosomes. During this process, targeted cytoplasmic constituents are isolated from the rest of the cell within a double-layered membrane vesicle known as an autophagosome. The autophagosome then fuses with a lysosome and its cargo is degraded and recycled. Autophagy has been implicated in a number of fundamental biological processes including cellular homeostasis, aging, immunity, protein quality control, as well as in many different diseases like cancer, cardiomyopathy, neurodegeneration, infectious diseases and hepatic encephalopathy. While a decreased autophagic activity may intervene with protein degradation, its increased activity appears to facilitate the clearance of aggregation-prone intracytoplasmic pathogenic proteins like mutant huntingtin or α-synuclein, and pathogens, as well as to promote neuronal survival in a wide range of disease models. However, excessive levels of autophagic activity can be pernicious as well and lead to cell death, demonstrating the importance of the regulation of autophagy for cell fate determination. Autophagy can be induced by different stress protein systems, such as thermal stress, oxidative stress and endoplasmic reticulum stress. Mild endoplasmic reticulum stress has been shown to induce cytoprotective response which protects the cell against a stronger insult in ischemia/hypoxia models. Mammalian autophagy is constitutively active in neurons and it is essential for the maintenance of neuronal function. The suppression of its activity in neurons results in severe neurodegenerative disorders. Further studies of autophagy-related pathways, ATG genes and their precise contribution during the biogenesis of double-membrane vesicles, ER stress, selective types of autophagy and their emerging importance as a quality control to maintain cellular homeostasis, will greatly expand our understanding of autophagy in the neuropathogenesis, while development of new experimental approaches, methods and sophisticated pharmacological tools may provide drug targets identification and their rational design in the treatment of a wide range of age-related diseases and both pediatric and adult neurodegenerative diseases, and informations gained from these studies may be useful for the treatment of many other autophagy-related diseases, like cancer, cardiovascular and pulmonary diseases, infectious and autoinflammatory disorders.