<p>Stem cells (SC) based therapies are proving to be the mainstay of regenerative medicine. Despite the significant potential, direct grafting or implantation of SCs for regenerative therapy encounters various translational roadblocks such as paucity of implantable cells, decreased potency, cell death post-implantation, cell damage caused by the pre-existing inflammation and immune rejection. Hence, an emerging avenue is cell-free approach; use of SC secretome. Although priming approaches based on pharmacological molecules/chemicals, cytokines and growth factors are being explored to elicit enhanced secretome production, the potential concerns include the need for continuous replenishment and potential chemical contamination during secretome isolation. To alleviate these concerns, various non-pharmacological approaches for invigorating SCs are also being investigated and among these, use of photobiomodulation (PBM) has garnered considerable interest. Notwithstanding the positive outcomes, standardized parameters are yet to be established for reproducible results. Moreover, the mechanisms of PBM based SC stimulation and secretome production are poorly elucidated and significant knowledge gaps exist on influence of cell type, culture conditions on PBM. This review aims to provide insight into the current status of this emerging field emphasizing on novel avenues and potential challenges for clinical translation. We also summarize the studies on PBM based proliferation, differentiation and secretome production according to SC cell type and culture conditions. Further, as a fixed PBM based protocol for SC proliferation, differentiation and secretome is lacking, the knowledge on functional targets and pathways in PBM based SC stimulation needs upgradation. Consequently, putative mechanisms for PBM based SC secretome have been proposed.</p>