Personalized nutrition has been traditionally based on the adjustment of food and diet according to individual needs and preferences. At present, this concept is being reinforced through the application of state-of-the-art high-throughput technologies to help understand the molecular mechanisms underlying a healthy state. This knowledge could enable the adjustment of general dietary recommendations to match the needs of specific population groups based on their molecular profiles. The optimal development of evidence-based nutritional guidance to promote health requires an adequate assessment of nutrient bioavailability, bioactivity, and bioefficacy. To achieve this, reliable information about exposure to nutrients, their intake, and functional effects is required; thus, the identification of valid biomarkers using standardized analytical procedures is necessary. Although some nutritional biomarkers are now successfully used (eg, serum retinol, zinc, ferritin, and folate), a comprehensive set to assess the nutritional status and metabolic conditions of nutritional relevance is not yet available. Also, there is very limited knowledge on how the extensive human genetic variability influences the interpretation of these biomarkers. In this context, nutrigenomics seems to be a promising approach to identify new biomarkers in nutrition, through an integrative application of transcriptomics, proteomics, metabolomics, epigenomics, and nutrigenetics in human nutritional research.