In recent years, increasing interest on the effects of dietary components on epigenetic processes and, consequently, on the regulation of gene expression and metabolic responses has led clinical efforts worldwide to approach obesity. When inadequate, food consumption leads to chronic and non-communicable diseases (CNCD) including obesity. Among the dynamic changes in cellular responses by nutritional interventions, epigenetic control represents a master regulator underlying both positive and negative effects of diet on body mass, including DNA methylation, histone post-translational modifications and microRNA expression signatures. Indeed, mechanistical studies of the relationship between environment, diet and differential epigenetic landscapes are gaining attention on functional pathways involved in cell growth, DNA-repair, lipogenesis, senescence, inflammation, tumor suppression, apoptosis and oncogenesis. Being the dynamic interplay between epigenetics and obesity so complex, moreover considering a detrimental environment context, this chapter will discuss the state-of-the-art evidence showing the pollution impact on the different epigenetic mechanisms regulating an obese phenotype, and how these molecular events determine the organic interplay upon metabolic alterations, and finally we will introduce recent epidrugs and biocompounds of therapeutic interests due to their potential to modulate and even revert obesity-inducing epigenetic mechanisms.