Allergic diseases are prototypic examples for gene × environment-wide interactions. This review considers the current evidence for genetic and epigenetic mechanisms in allergic diseases and highlights barriers and facilitators for the implementation of these novel tools both for research and clinical practice.The value of whole-genome sequencing studies and the use of polygenic risk score analysis in homogeneous well characterized populations are currently being tested. Epigenetic mechanisms are known to play a crucial role in the pathogenesis of allergic disorders, especially through mediating the effects of the environmental factors, well recognized risk modifiers. There is emerging evidence for the immune-modulatory role of probiotics through epigenetic changes. Direct or indirect targeting of epigenetic mechanisms affect expression of the genes favouring the development of allergic diseases and can improve tissue biology. The ability to specifically edit the epigenome, especially using the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 technology, holds the promise of enhancing understanding of how epigenetic modifications function and enabling manipulation of cell phenotype for research or therapeutic purposes.Additional research in the role of genetic and epigenetic mechanisms in relation to allergic diseases' endotypes is needed. An international project characterizing the human epigenome in relation to allergic diseases is warranted.