Respiratory diseases present a very high prevalence in the general population, with an increase in morbidity, mortality and health-care expenses worldwide. They are complex and het-erogeneous pathologies that may present different pathological facets in different subjects, often with personal evolution. Therefore, there is a need to identify patients with similar characteristics, prognosis or treatment, defining the so-called phenotype, but also to mark specific differences within each phenotype, defining the endotypes. Biomarkers are very useful to study respiratory phenotypes and endotypes. Metabolomics, one of the recently introduced “omics”, is becoming a leading technique for biomarker discovery. For the airways, metabolomics appears to be well suited as the respiratory tract offers a natural matrix, the Exhaled Breath Condensate (EBC), in which several biomarkers can be measured. In this review, we will discuss the main methodological issues related to the application of Nuclear Magnetic Resonance (NMR) spectroscopy and Mass Spectrometry (MS) to EBC metabolomics for investi-gating respiratory diseases. © 2020 Bentham Science Publishers.