Mechanisms of the Development of Allergy (MeDALL) was a European Union-Seventh Framework Programme for Research and Technological Development project aimed to apply the systems medicine approach to improve the understanding of allergic diseases. It was based on existing birth cohorts to redefine classical phenotypes and identify novel phenotypes of immunoglobulin (Ig)E-associated asthma, allergic rhinitis and dermatitis. The project included a wide range of population-based, clinical and mechanistic studies applying systems medicine. MeDALL demonstrated the existence of the multimorbidity of eczema, rhinitis, and asthma both in IgE-sensitized and non-sensitized children and integrated the evidence on multimorbidities and polysensitization in a new framework of allergic diseases. Innovative approaches included unsupervised statistical modelling, computational analysis of the topology of the protein interaction network and the IgE MeDALL allergen-chip. Mechanistic studies included testing candidate biomarkers, epigenetics, and transcriptomics. Assessment of individual and environmental factors included puberty, maternal smoking and pregnancy.