Metabolic health and immune function are intimately connected via diet and the microbiota. Nearly 90% of all immune cells in the body are associated with the gastrointestinal tract and these immune cells are continuously exposed to a wide range of microbes and microbial‐derived compounds, with important systemic ramifications. Microbial dysbiosis has consistently been observed in patients with atopic dermatitis, food allergy and asthma and the molecular mechanisms linking changes in microbial populations with disease risk and disease endotypes are being intensively investigated. The discovery of novel bacterial metabolites that impact immune function is at the forefront of host‐microbe research. Co‐evolution of microbial communities within their hosts has resulted in intertwined metabolic pathways that affect physiological and pathological processes. However, recent dietary and lifestyle changes are thought to negatively influence interactions between microbes and their host. This review provides an overview of some of the critical metabolite‐receptor interactions that have been recently described, which may underpin the immunomodulatory effects of the microbiota, and are of relevance for allergy, asthma and infectious diseases.