This special issue on 'Translational Biophotonics' was initiated when COVID-19 started to spread worldwide in early 2020, with the aim of introducing the advances in optical tools that have the ability to transform clinical diagnostics, surgical guidance, and therapeutic approaches that together can have a profound impact on global health. This issue achieves this goal comprehensively, covering various topics including optical techniques for clinical diagnostics, monitoring and treatment, in addition to fundamental studies in biomedicine.