Biomarkers such as clinical characteristics and laboratory indices have been widely used in many respiratory diseases, such as chronic airway diseases, lung infection, lung cancer and acute respiratory distress syndrome. As such, various non‐invasive and invasive samples, such as blood, urine, induced sputum, bronchoalveolar lavage fluid and lung biopsy are currently being collected. Omics‐based discovery strategies facilitate the identification of next‐generation candidate biomarkers. The identification and integration of multiple omics biomarkers (genomics, epigenomics, proteomics, metabolomics and radiomics) can answer many unsolved questions about respiratory diseases. The ultimate realization of the translation of novel biomarkers into clinical practice is a major challenge because good biomarkers must be sensitive, technically feasible, non‐invasive, non‐expensive and most importantly, validated. The four stages of clinical trial design in the development of biomarkers are also discussed. The concept of systems biology not only focuses on novel molecular biomarkers but also integrates clinical, laboratory and omics information as a whole. Finally, developing multiple biomarker panels is a goal to improve the healthcare of respiratory diseases.