The 2016 Nobel Prize in Physiology or Medicine was awarded to Japanese scientist Yoshinori Ohsumi for his groundbreaking discoveries elucidating the molecular mechanisms underlying autophagy, a fundamental cellular process of self-degradation and recycling. Through elegant genetic screens in baker’s yeast (Saccharomyces cerevisiae) conducted in the early 1990s, Ohsumi identified the key genes essential for autophagy, revealing a sophisticated intracellular machinery that enables cells to degrade and recycle their own components. This review provides a comprehensive analysis of Ohsumi’s seminal contributions, the molecular architecture of the autophagy pathway, and its profound clinical implications for aging, cancer, neurodegenerative diseases, and metabolic disorders. We examine the dual role of autophagy as both a tumor suppressor and tumor promoter, its critical involvement in maintaining neuronal homeostasis, and its dysregulation in conditions such as diabetes. The discoveries honored by this Nobel Prize have fundamentally transformed our understanding of cellular quality control and opened new therapeutic avenues for the treatment of diverse human pathologies.