Healthcare research and delivery in the modern era of molecular and personalized medicine requires reliable quantification of biomedical imaging data. Imaging biomarkers are of considerable interest in evidence-based clinical decision-making and for therapeutic development. The demand for quantitative results from imaging studies will increase as treatment decisions are driven by such results. Once achieved, reliable imaging quantification will lead to validation and qualification of imaging biomarkers for use in clinical trials, drug development and clinical decision-making.There are several sources of bias and variance in the quantitative results obtained from clinical images. Achieving reliable extraction of quantitative results from imaging scans requires a standardized approach to data acquisition, process and interpretation. Thus the entire chain involved in producing a clinical image must be approached from a systems-engineering perspective. Considerable work is needed to validate specific metrics, improve standardization across vendor platforms, and educate imaging physicians about the reliability of QI. An additional challenge is the continual state of technological advancement that occurs in medical imaging hardware and software. Thus, the quantitative accuracy of medical images has to be continually re-assessed and the standardization requirements have to be periodically updated. This continuous, systematic appraisal of accuracy and precision is crucial to maintain confidence in quantitative interpretations. Broad multidisciplinary stakeholder collaboration is needed to achieve cross-industry consensus on and adoption of quantitative imaging biomarkers.In response to the need for reliable and reproducible imaging biomarkers, the RSNA in 2007 organized the Quantitative Imaging Biomarkers Alliance (QIBA, http://rsna.org/QIBA_.aspx) whose mission is to improve the value and practicality of quantitative imaging biomarkers by reducing variability across devices, patients and time. One of QIBA’s goals is to have imaging scanners be engineered as measuring instruments in addition to imaging instruments. The QIBA initiative creates a forum for an organized and effective cooperative effort among stakeholders (1). QIBA participants span a wide range of expertise including clinical practice, clinical research, physics, statistics, engineering, marketing, regulatory, pharmaceutical, and computer science. QIBA employs a consensus-driven, systematic approach to produce a QIBA Profile, i.e., a systems-engineering document that includes one or more QIBA Claims and specifications for the image acquisition and processing necessary to achieve the QIBA Claim. Profiles take into consideration technical (product-specific) standards, user activities, and relationship to a clinically meaningful metric such as therapeutic response or other patient outcome measure. QIBA is also developing a conformance program to allow vendors and users to determine whether equipment and other “actors” are QIBA-Profile-conformant, using QIBA-branded or recommended phantoms (test objects), data sets, software and other tools. QIBA Profiles are based on published data whenever such data are available and on expert consensus opinion where no data exist. Under a research contract from the National Institutes of Health QIBA funds about 12 “groundwork projects” per year to collect data for specifications in the QIBA Profiles. There are QIBA committees developing Profiles for biomarkers that involve all four of the major imaging modalities: CT, MR, nuclear medicine and ultrasound. QIBA has completed three Profiles (CT Volumetry; DCE-MRI; and FDG-PET) and has several in development. Examples of QIBA Profiles can be found at http://rsna.org/QIBA_Protocols_and_Profiles.aspx.The focus of a QIBA Profile is to reduce bias and improve reproducibility (precision) of a quantitative result from an imaging examination. For each biomarker, QIBA Biomarker Committees coordinate the research and other groundwork to achieve resolution of the scientific questions. The goal is to establish processes and QIBA Profiles that will lead to acceptance of quantitative imaging biomarkers by the imaging community, clinical trial industry, and regulatory agencies as proof of biology, proof of changes in pathophysiology, and surrogate end-points for changes in the health status of patients. QIBA created a Metrology Working Group to provide expert advice on terminology and methodology relevant to QIBs. The output of their workshops and conference calls is a series of five manuscripts published as a special edition of the journal Statistical Methods in Medical Research and can be downloaded from the RSNA QIBA website. A publication describing a summary of the metrology standards is listed in the References (2). Although based primarily in the USA, international participation in QIBA is substantial. The European Society of Radiology (ESR) has established the European Imaging Biomarkers Alliance (EIBALL), and the leaders of the Japan Radiological Society (JRS) have created a Steering Committee for QIBA Japan activities.