Obesity has reached epidemic proportions globally. Although modern adoption of a sedentary lifestyle coupled with energy-dense nutrition is considered to be the main cause of obesity epidemic, genetic preposition contributes significantly to the imbalanced energy metabolism in obesity. However, the variants of genetic loci identified from large-scale genetic studies do not appear to fully explain the rapid increase in obesity epidemic in the last four to five decades. Recent advancements of next-generation sequencing technologies and studies of tissue-specific effects of epigenetic factors in metabolic organs have significantly advanced our understanding of epigenetic regulation of energy metabolism in obesity. The epigenome, including DNA methylation, histone modifications, and RNA-mediated processes, is characterized as mitotically or meiotically heritable changes in gene function without alteration of DNA sequence. Importantly, epigenetic modifications are reversible. Therefore, comprehensively understanding the landscape of epigenetic regulation of energy metabolism could unravel novel molecular targets for obesity treatment. In this review, we summarize the current knowledge on the roles of DNA methylation, histone modifications such as methylation and acetylation, and RNA-mediated processes in regulating energy metabolism. We also discuss the effects of lifestyle modifications and therapeutic agents on epigenetic regulation of energy metabolism in obesity.