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Wheezing in preschool children is a very common symptom. An adequate prediction of asthma in these children is difficult and cannot be reliably assessed with conventional clinical tools. The study of potential predictive biomarkers in various media, ranging from invasive sampling (e.g. bronchoscopy) to non-invasive sampling (lung function testing and exhaled breath analysis) was comprehensively reviewed. The evolution in biomarker discovery has resulted in an 'omics' approach, in which hundreds of biomarkers in the field of genomics, proteomics, metabolomics and 'breath-omics' can be simultaneously studied. First results on gene expression and exhaled breath profiles in predicting an early asthma diagnosis are promising. However, many hurdles need to be overcome before clinical implementation is possible. In order to reliably predict asthma in a wheezing child, probably a holistic approach is needed, combining clinical information with blood sampling, lung function tests, and potentially exhaled breath analysis. The further development of predictive, non-invasive biomarkers may eventually improve an early asthma diagnosis in wheezing preschool children, and assist clinicians in early treatment decision-making. This article is protected by copyright. All rights reserved.