In lung cancer, as well as in other malignancies, the so-called “liquid biopsy” is quickly moving from research into clinical practice. Although it has not yet reached its full potential, the “liquid biopsy” is no longer a promise but a reality that is allowing a better monitoring and treatment selection of cancer patients in many hospitals and oncology departments. We can already envision a day when “liquid biopsy” tests will be as common and useful as imaging techniques and “standard” biopsies, offering invaluable prognostic and predictive information. The objective of this special issue of Translational Lung Cancer Research (TLCR) is to offer an overview of this exciting area, with a particular emphasis on the clinical utility of the so-called “liquid biopsy” and the diversity of applications, methodologies and information that can be derived from it.