Obesity is highly prevalent in developed countries and contributes to a substantial burden of morbidity and mortality. Increased adiposity is often accompanied by comorbidities such as insulin resistance, type 2 diabetes, hypercholesterolemia, cardiovascular disease, fatty liver disease, low-grade inflammation, immune disorders, endocrine complications, and sleep apnea, which may require specific dietary and pharmacological interventions. The current obesity epidemic requires a better understanding of the underlying mechanisms through which genetic and epigenetic factors interact to determine metabolic characteristics. Epigenetic studies are dynamic; tags with reversible potential can be influenced by genetics and environment attributing phenotypic variations. There are large knowledge gaps regarding how human epigenetic changes are related to obesity and its consequences. Therefore, the present study elucidates the role of epigenetics in the etiology of obesity. Recent studies suggest that the epigenetic regulation of gene expression (DNA methylation and histone modifications) could be a major contributor to the variation of susceptibility to diseases such as obesity. The identification of genes that determine obesity susceptibility can provide information on the pathophysiological mechanisms underlying body weight regulation, food intake control and fat distribution, which in turn can lead to new approaches to treatment and prevention of obesity.