In the last few years, the idea of food and nutrition has undergone radical changes. The paradigm defining food as a simple source of energy and body mass has evolved in a novel concept, in which nutrients can exert specific functions directly linked to human health. Several edibles contain biological active compounds that influence cellular, metabolic and physiologic processes. A variety of dietary compounds have been associated with specific effects and mechanisms of action, often involving epigenetic modifications and gene expression changes. DNA methylation, histone modifications and the activity of non-coding RNAs control chromatin condensation state, allowing the interaction of DNA with transcription factors required for transcriptional activation. Some metabolites act as substrates of key chromatin remodeling factors or compete with other substrates, influencing their catalytic activity. The quantity and quality of macronutrients assumed by diet offers a possible mechanism of interaction between the body and its environment. A number of biological compounds are known to interact with the epigenome. Folic acid, methionine, choline and other B group vitamins are an important source of one-carbon groups required for methylation of histone proteins and non-histone chromatin remodeling factors. Other compounds like polyphenols, including resveratrol, curcumin and quercetin exert a multitude of biological activities. Furthermore, these compounds can influence DNA methyltransferases, the enzymes responsible for DNA methylation. Dietary interventions aimed to maximize potential health benefits derived from nutrition have shown that dietary regimens can be very effective for prevention and treatment of several diseases. Calorie restriction, protein restriction, fast mimicking diets or time restricted feeding have shown to have significant effects on health. Food quality is crucial for the activity of biological compounds and their potential health benefits. Diets rich in animal-derived proteins are associated with higher rates of mortality compared to diets based on plant-derived proteins.