Exposure to nutritional imbalance during early life can influence disease risk lifelong and across generations. In this long-term conditioning, epigenetics constitutes a key mechanism. They bridge environmental cues and the expression of genes involved in the setting of long-standing biological regulations in numerous organs and species. Epigenetic marks are proposed as innovative diagnostic biomarkers and potential targets in the prevention of diseases. However, a number of uncertainties make them difficult to use in clinical approaches in the context of early exposure to nutritional challenge. In conclusion, active investigations in this field are still needed before clinical applications are considered.