Highlights • Adipose tissue secretes bioactive peptides/proteins, known as adipocytokines. • Adipocytokines are involved in the pathogenesis of diseases in nearly all body systems. • Adipocytokines had an impact on metabolic, oncologic, and rheumatologic disorders. Introduction Adipose tissue secretes various bioactive peptides/proteins, immune molecules and inflammatory mediators which are known as adipokines or adipocytokines. Adipokines play important roles in the maintenance of energy homeostasis, appetite, glucose and lipid metabolism, insulin sensitivity, angiogenesis, immunity and inflammation. Enormous number of studies from all over the world proved that adipocytokines are involved in the pathogenesis of diseases affecting nearly all body systems, which raises the question whether we can always blame adipocytokines as the triggering factor of every disease that may hit the body. Objective Our review targeted the role played by adipocytokines in the pathogenesis of different diseases affecting different body systems including diabetes mellitus, kidney diseases, gynecological diseases, rheumatologic disorders, cancers, Alzheimer’s, depression, muscle disorders, liver diseases, cardiovascular and lung diseases. Methodology We cited more than 33 recent literature reviews that discussed the role played by adipocytokines in the pathogenesis of different diseases affecting different body systems. Conclusion More evidence is being discovered to date about the role played by adipocytokines in more diseases and extra research is needed to explore hidden roles played by adipokine imbalance on disease pathogenesis.