As each individual person differs from the next in multiple ways, it is a beguiling idea that our individual nutritional needs also differ. In support of this idea, findings from nutritional intervention studies provide ample evidence of considerable interindividual variation in response to the same dietary exposure. We have a limited understanding of the mechanisms responsible for this variation but, following sequencing of the human genome, the role of genes in explaining interindividual differences has been centre stage. In addition, evidence of diet–gene interactions that influence phenotype, including health, emphasises the importance of both nature and nurture. Eating patterns are major determinants of health, so public health advice to reduce the risk of common complex diseases focuses on diet. However, most dietary interventions are relatively ineffective and personalised approaches that tailor the intervention to the individual may be more acceptable and more effective. That idea was tested in the Food4Me study in which adults from seven European countries were randomised to one of four treatment groups in an internet-delivered dietary intervention. Compared with the Control (standardised healthy eating advice), those people randomised to a personalised nutrition intervention had bigger, sustained changes, in eating behaviour after 6 months. However, including more complex phenotypic and/or genotypic information in developing the personalised nutrition advice had no added benefit. Research in personalised nutrition is broadening its scope to consider effects mediated by the gut microbiome as well as multiple aspects of genotype and phenotype. Such research has the potential to explain interindividual differences in the response to specific dietary factors and may provide a scientific basis for more refined approaches to personalised nutrition. However, if this research is to make a significant contribution to improving public health, it will need to address the psychological, social, economic and cultural factors that influence eating patterns to ensure that advice is converted into action and that improved dietary habits are sustained in perpetuity.