This review explores the nature of metabolic syndrome (MS), a cluster of related but distinct pathologies that collectively affect a significant portion of the global population. The MS is characterized by its "human" nature, reflecting the interplay between environmental and internal factors, particularly diet and lifestyle, which have evolved in concert with human society. The review highlights the close interdependence of MS components, emphasizing their syndromic development and the impact on energy handling and partitioning. Key theories on the origin and development of MS, including the role of hepatic steatosis, type 2 diabetes, and obesity, are discussed. The influence of sex and its biological consequences, as well as the role of inflammation, are also examined. The review suggests that MS may be a unique, monophyletic complex biological control system, and it considers additional perspectives on the treatment of this multifaceted human disease. The text underscores the complexity of MS, its impact on various organ systems, and the need for a comprehensive understanding of its underlying mechanisms to develop effective treatments.This review explores the nature of metabolic syndrome (MS), a cluster of related but distinct pathologies that collectively affect a significant portion of the global population. The MS is characterized by its "human" nature, reflecting the interplay between environmental and internal factors, particularly diet and lifestyle, which have evolved in concert with human society. The review highlights the close interdependence of MS components, emphasizing their syndromic development and the impact on energy handling and partitioning. Key theories on the origin and development of MS, including the role of hepatic steatosis, type 2 diabetes, and obesity, are discussed. The influence of sex and its biological consequences, as well as the role of inflammation, are also examined. The review suggests that MS may be a unique, monophyletic complex biological control system, and it considers additional perspectives on the treatment of this multifaceted human disease. The text underscores the complexity of MS, its impact on various organ systems, and the need for a comprehensive understanding of its underlying mechanisms to develop effective treatments.