There is a great interest in developing biomarkers to enable precision medicine and improve health outcomes of patients with chronic obstructive pulmonary disease (COPD). However, biomarker development is extremely challenging and expensive, and translation of research endeavors to date have been largely unsuccessful. In most cases, biomarkers fail owing to poor replication of initial promising results in independent cohorts and/or inability to transfer the biomarker from a discovery platform to a clinical assay. Ultimately, new biomarker assays must address the following 5 “SAVED” questions for optimal clinical translation. They include: is the biomarker likely to be: 1) Superior (will the test outperform current standards?); 2) Actionable (will the test change patient management?); 3) Valuable (will the test improve patient outcomes?); 4) Economical (will the implementation of the biomarker in the target population be cost-saving or cost-effective?); and 5) clinically Deployable (is there a pathway for the biomarker and analytical technology to be implemented in a clinical laboratory?). In this paper, we review some of the major barriers to biomarker development in COPD and provide possible solutions to overcome these limitations, enabling translation of promising biomarkers from discovery experiments to clinical implementation.