Autophagy has emerged as a central regulator of cellular homeostasis, integrating metabolic state, stress responses, and cell fate decisions. Once regarded primarily as a cytoprotective housekeeping process, autophagy is now understood as a context-dependent pathway whose dysregulation can actively contribute to the initiation and progression of major civilization diseases, including cancer, neurodegeneration, metabolic disorders, and organ-specific complications. In parallel, advances in metabolic biology have revealed highly dynamic and adaptable networks that closely intersect with autophagic regulation. This Special Issue of The European Journal of Pharmacology provides a unified conceptual framework for understanding how the autophagy-metabolism axis shapes disease pathophysiology and therapeutic response. Bringing together integrative reviews and original research articles, the collection highlights how autophagy can be both protective and pathogenic, depending on disease stage, tissue context, and environmental stress. Contributions span neurodegenerative disorders, cancer signalling and chemoresistance, metabolic complications, and emerging therapeutic strategies, including pathway-targeted drugs, metabolic modulators, natural compounds, and advanced delivery platforms. Collectively, this volume positions autophagy not as an isolated pathway but as a central, actionable interface between metabolism and pharmacological intervention, underscoring the need for precise, context-aware modulation in future therapeutic designs.
