A main challenge in nutritional studies is the valid and reliable assessment of food intake, as well as its effects on the body. Generally, food intake measurement is based on self-reported dietary intake questionnaires, which have inherent limitations. They can be overcome by the use of biomarkers, capable of objectively assessing food consumption without the bias of self-reported dietary assessment. Another major goal is to determine the biological effects of foods and their impact on health. Systems analysis of dynamic responses may help to identify biomarkers indicative of intake and effects on the body at the same time, possibly in relation to individuals’ health/disease states. Such biomarkers could be used to quantify intake and validate intake questionnaires, analyse physiological or pathological responses to certain food components or diets, identify persons with specific dietary deficiency, provide information on inter-individual variations or help to formulate personalized dietary recommendations to achieve optimal health for particular phenotypes, currently referred as “precision nutrition.” In this regard, holistic approaches using global analysis methods (omics approaches), capable of gathering high amounts of data, appear to be very useful to identify new biomarkers and to enhance our understanding of the role of food in health and disease.