Dietary fatty acid intake has a profound influence on the lipid composition of cell membranes as well as the membranes of mitochondria. Professor Carlo Agostoni reviews the far-reaching effects of dietary fatty acids on modulating immunity. What are the mechanisms through which this occurs? Fatty acids are important components of lipid mediators, such as PIP3 and ceramide. They can also influence the action of transcription factors, such as the PPARs, which in turn affect gene expression and biological response. Agostoni extends these mechanistic findings to the clinic, by reviewing the data from adults and children across a variety of indications, such as rheumatoid arthritis and non-alcoholic fatty liver disease. Individual genetic variation in the FADS genes adds a further layer of complexity to clinical findings. How can we explain the effects of diet, genetic background, and phenotype? Agostoni proposes a functional model that explains the interaction between these factors, using it to clarify the influence of lifestyle on health outcomes such as the relationship between maternal smoking and alcohol intake on infant growth.