Interstitial lung disease (ILD) comprises a heterogenous group of diffuse lung disorders that commonly result in irreversible pulmonary fibrosis. While idiopathic pulmonary fibrosis (IPF) is the prototypical progressive fibrosing ILD (PF-ILD), a high proportion of patients with other ILD subtypes develop a PF-ILD phenotype. Evidence exists for shared pathobiology leading to progressive fibrosis, suggesting that biomarkers of disease activity may prove informative across the wide spectrum of ILDs. Biomarker investigation to date has identified a number of molecular markers that predict relevant ILD endpoints, including disease presence, prognosis, and/or treatment response. In this review, we provide an overview of potentially informative biomarkers in patients with ILD, including those suggestive of a PF-ILD phenotype. We highlight the recent genomic, transcriptomic, and proteomic investigations that identified these biomarkers and discuss the body compartments in which they are found, including the peripheral blood, airway, and lung parenchyma. Finally, we identify critical gaps in knowledge within the field of ILD biomarker research and propose steps to advance the field toward biomarker implementation.