Reliability and reproducibility of results are crucial in the development of medical technology, and it is time for those involved in supporting and implementing research to devise standards and related phantoms for success in biophotonics. Fragmented efforts must be consolidated, and they must be enhanced with contributions by people and organizations ranging from technology developers to clinicians, and from industry to funding agencies. In clinical chemistry, large multilaboratory initiatives for standardization have built a foundation for microbiological and pharmaceutical breakthroughs. For biophotonics, a similar foundation is needed, which would speed up the development of new devices and their deployment. The biological variability between individual persons must be disentangled from the technical variability between instruments. Many problems in clinical applications are directly related to basic physics (e.g., measuring through skins of different colors and thicknesses, reaching the brain noninvasively through the scalp and skull, etc.), and living tissue can safely be exposed to only limited amounts of energy. Once a problem is properly formulated, quantifying and comparing basic performances of various types of instruments can more objectively be achieved. The comparability and even reliability of clinical studies could be improved if the applied instruments were characterized on recognized gold standards and tested to maintain performance. Also, machine learning would greatly benefit from the adoption of standardized measurements on well-defined reference materials and/or phantoms, as well as from resulting quality-controlled open-access data sets. Proper protocols would be the basis for industrial standards and quality tests, offering a transparent reference framework for manufacturers, medical professionals, health care insurers, and governments. The international community needs to formulate aspects of clinical problems in objective physical terms, agree upon protocols identifying key figures of merit, create transferable tissue-simulating phantoms, run round-robin tests for instrument comparison, and populate a well-annotated database of optical tissue properties. Multilaboratory initiatives should collaborate with national and international institutes for standards and measurement technology and with standards-issuing bodies. Funding agencies and governmental bodies would also play a vital role. The driving force should be improving patient care while establishing a long-term vision to lay solid foundations for the growth of biophotonics techniques. The European Commission, Photonics21, and EPIC (the European Photonics Industry Consortium) have created a multipartner ecosystem that has produced spontaneous long-term initiatives beyond the boundaries of specific projects or national borders. Three protocols for performance assessment of diffuse optics instruments (MEDPHOT, BIP, and nEUROPt) developed in European projects have become state of the art in the characterization of instrumentation in this field, further highlighted by the ongoing BitMap exercise for cross-comparison of diffuse optics instruments and deployment of open data involving over 30 instruments from 12 institutions. Related activities included the characterization of the components of a liquid reference phantom with agreement within 2% to 3% for the related opti-cal absorption and scattering properties, as well as a multi- institution campaign for the compilation of in vivo brain optical properties. The time is now to coordinate these spontaneously grown initiatives — which are often focused on specific isolated applications — and to unite the various actors (physicists, clinicians, regulatory bodies, funding agencies, industry, and patient associations) to jointly draft the path for the future. This was the goal of a foresight workshop, promoted by the European Commission, which gathered various players in September in Brussels on the topic of “Performance Assessment and Standardization in Biophotonics.” Inspired by existing collaborative schemes from other disciplines (such as high-energy physics and astrophysics), we are encouraged to pursue cross-validation, open data, multi-institution analysis, reference standards, consensus conferences, double-checks of scientific results, and joint efforts on concerted experiments. Scientific advancements are built upon previous foundations. During the coming decades, biophotonics will revolutionize health care as electronics did during the past century. It is necessary to promote not only disruptive breakthrough discoveries, but also the subsequent consolidation of knowledge to rapidly increase technology readiness levels and decrease costs for producing advanced medical technologies. Meet the authors Antonio Pifferi is a full professor of physics at Politecnico di Milano and works on novel biophotonics tools for clinical diagnostics based on time-domain diffuse optics; email: antonio.pifferi@polimi.it. Fokko Wieringa is principal scientist at imec the Netherlands and associate professor at Maastricht University. He develops medical devices and co-authors international ISO/IEC standards. Srirang Manohar is full professor and chair of multimodality medical imaging at the University of Twente in the Netherlands and develops imaging technologies based on photoacoustics and ultrasound. Paola Taroni is full professor of physics at Politecnico di Milano and works on development of optical diagnostic methods, with special consideration for translational aspects. Sarah Bohndiek is a reader in biomedical physics at the University of Cambridge. She develops novel imaging approaches for tumor microenvironments and facilitates clinical translation of new biophotonics methods. Heidrun Wabnitz is senior scientist at Physikalisch-Technische Bundesanstalt Berlin and works on time-domain methods in diffuse optics, device performance characterization, and standardization.