Interstitial lung diseases (ILD) are protean conditions with substantial overlap in terms of diagnosis, prognostic evaluation, and management. However, the management of idiopathic pulmonary fibrosis is different from that of more immunologically driven ILD patterns, such as ILD associated with connective tissue diseases. It is important to provide accurate diagnosis and patient selection for prognostication and timely treatment, preferably at baseline. Validated non-invasive biomarkers fulfilling these unmet clinical needs are warranted. Although no ILD biomarker has been adopted in clinical practice so far, advancements in this field have been achieved, especially with the implementation of high-throughput techniques and clinical-laboratory multi-parametric panels. This review focuses on selected validated and/or potentially interesting biomarkers investigated in the peripheral blood and lung tissue of patients with ILD. Current issues and future directions in various aspects of ILD biomarkers research and its clinical application are explored.