Introduction: The role of low level laser/light therapy (LLLT) for the management of oral mucositis (OM) has been evaluated in a number of studies including randomised clinical trials (RCTs). Subsequently the MASCC/ISOO clinical practice guidelines have included LLLT as a recommended treatment option for the prevention of OM in haematopoietic stem cell transplantation recipients conditioned with high-dose chemotherapy, with or without total body irradiation, and suggested its use for the prevention of OM in patients undergoing radiotherapy, without concomitant chemotherapy, for head and neck cancer. The mechanism of action, and optimal irradiation parameters and treatment dose have been reported in other pathologies but are not well defined in OM. Objectives: To assess the mechanisms of action, optimal irradiation parameters, and treatment dose. Methods: A systematic review was performed of in vitro and in vivo studies focusing upon mechanisms of action, and of irradiation parameters and dose used in RCTs of LLLT in OM. Results: We identified 12 papers addressing mechanism /and 19 RCTs. Studies provided evidence for a reduced inflammatory response (e.g., reduced COX-2 expression, reduced numbers of neutrophils), and improved wound healing (e.g., increased expression of growth factors, fibroblasts proliferation, increased angiogenesis). A dose response pattern could be established, although irradiation parameters appeared to be inconsistent. Conclusion: There is evidence for LLLT efficacy in OM management, but reporting of irradiation parameters needs improvement. More studies are needed to provide a better understanding of LLLT mechanisms in OM management.