The fundamental pathophysiologic response for the survival of all organisms is the process of wound healing. Inadequate or lack of healing constitutes the etiopathologic basis of many oral and systemic diseases. Among the numerous efforts to promote wound healing, biophotonics therapies have shown much promise. Advances in photonic technologies and a better understanding of light-tissue interactions, from parallel biophotonics fields such as in vivo optical imaging and optogenetics, are spearheading their popularity in biology and medicine. Use of high-dose lasers and light devices in dermatology, ophthalmology, oncology, and dentistry are now popular for specific clinical applications, such as surgery, skin rejuvenation, ocular and soft tissue recontouring, and antitumor and antimicrobial photodynamic therapy. However, a less well-known clinical application is the therapeutic use of low-dose biophotonics termed photobiomodulation (PBM) therapy, which is aimed at alleviating pain and inflammation, modulating immune responses, and promoting wound healing and tissue regeneration. Despite significant volumes of scientific literature from clinical and laboratory studies noting the phenomenological evidence for this innovative therapy, limited mechanistic insights have prevented rigorous and reproducible PBM clinical protocols. This article briefly reviews current evidence and focuses on gaps in knowledge to identify potential paths forward for clinical translation with PBM therapy with an emphasis on craniofacial wound healing. PBM offers a novel opportunity to examine fundamental nonvisual photobiological processes as well as develop innovative clinical therapies, thereby presenting an opportunity for a paradigm shift from conventional restorative/prosthetic approaches to regenerative modalities in clinical dentistry.