Visible blue light of 400–720 nm wavelength has demonstrated microbicidal activity, like ultraviolet (UV) light, on contaminated pathogens in biological materials in various health settings without harming the functional aspects of the treated biological material, unlike UV light. Given this promise of relative safety, blue light has been evaluated in various scenarios to see whether it can replace UV light to enhance biological safety without compromising the microbicidal efficacy. In this context, there has been a surge of interest in evaluating high intensity narrow spectrum (HINS) 405-nm blue light toward pathogen inactivation in ex vivo human platelet concentrates (PCs) stored in plasma for transfusion. The study goal is to test whether HINS 405-nm light is a viable alternative to currently available chemical/UV-based technologies in terms of effective pathogen inactivation with a better outcome on the functional performance of the light-treated PCs. This includes evaluation of the functions of the treated platelets and the plasma in which platelets are stored, as almost all pathogens relevant to the safety of PCs from transfusion-transmitted infections (TTIs) tend to be extra-platelet and reside in plasma. To date, the 405-nm light treatment was shown to successfully inactivate a variety of blood-borne pathogens in platelets and plasma without significantly impeding the functions related to hemostasis of the treated PCs. Hence, this chapter reviews the published literature on this topic for the readers to appreciate the potential of this technology for the safety of PCs from TTIs.