Obesity significantly increases the risk of cardiometabolic diseases, such as type 2 diabetes, dyslipidemia, hypertension, coronary heart disease, and stroke. Furthermore, obesity is recognized as a risk factor for non-alcoholic fatty liver disease (NAFLD). NAFLD is commonly associated with insulin resistance and is strongly related to metabolic syndrome. The main function of adipose tissue is to store excess calories in the form of triglycerides and to release them during fasting period. The expansion of adipose tissue from an imbalance between food intake and energy expenditure, which leads to produce a number of bioactive substances, known as adipokines. Autologous to adipokines, myokines from skeletal muscle and hepatokines from the liver also affect whole body metabolism through autocrine, paracrine, and endocrine actions. Both hepatokines and myokines are now considered promising therapeutic targets for the preventions and treatment of obesity and type 2 diabetes. The objective of this short talk is to review recent data for the role of adipokines, hepatokines, and myokines in association with metabolic syndrome and NAFLD.