Autophagy is an important homeostatic cellular recycling mechanism responsible for degrading injured or dysfunctional cellular organelles and proteins in all living cells. Aging is a universal phenomenon characterized by progressive deterioration of cells and organs due to accumulation of macromolecular and organelle damage. Growing evidences indicate that the rate of autophagosome formation and maturation and the efficiency of autophagosome/lysosome fusion decline with age. Dysfunctional autophagy has also been observed in age-related diseases. Autophagy disruption resulted accumulation of mutated or misfolded proteins is the essential feature of neurodegenerative disorders. However, in cancers, fibroproliferative diseases or cardiovascular diseases, autophagy can play either a protective or destructive role in different types of disease, and even in different stages of the same disease. The review will discuss the cellular and molecular mechanisms of autophagy and its important role in the pathogenesis of aging and age-related diseases, and the ongoing drug discovery strategies for therapeutic intervention.