Our picture of allergy is changing. For one thing there is a dramatic rise in prevalence. Eczema, hay fever, asthma, and potentially life-threatening allergies to certain foods, drugs or other substances, have become alarmingly common: the World Allergy Organization White Book on Allergy 2011–2012 estimates that about 30–40% of the world's population is affected by one or more allergic conditions.

As allergies spread, our understanding of them is changing. For 40 years, from its first identification in the 1960s, immunoglobulin E (IgE) was the focus of the field. As the physiological processes of hypersensitive reaction were described, chemical mediators identified and drivers of those mechanisms pinned down, it began to look as though control of the IgE pathways would open the way to allergy prevention and effective therapies. Epidemiology could also expect more evidence from geneticists equipped with new tools for hypothesis-free association studies thanks to advances in genome sequencing (page S10). This Outlook, however, is not a triumphant account of strategies that overcame allergy. Recent exploration of the complexities of the adaptive immune system has turned some assumptions about allergies upside down, and researchers are swimming in unfamiliar waters.

Asthma, for instance, develops and responds in many different ways, not all triggered by allergy. It is better understood not as one disease, but many (page S20). Defects in skin and other epithelial barriers, once considered as symptoms of allergy, are being re-evaluated as potential primary causes (page S12). And, while environmental and lifestyle changes have been linked to the rising prevalence of allergy (page S2), attention to the role of gut-dwelling microbes has given a new dimension to the concept of a crucial balance toppled, with the human body seen not as a single organism but a complex ecosystem (page S5).

We are pleased to acknowledge the financial support of Nestlé Research Center in producing this Outlook. As always, Nature retains sole responsibility for all editorial content.