As a result of many years of research, the intricate cellular mechanisms of burn injury are slowly becoming clear. Yet, knowledge of these cellular mechanisms and a multitude of resulting studies have often failed to translate into improved clinical treatment for burn injuries. Perhaps the most valuable information to date is the years of clinical experience and observations in the management and treatment of patients, which has contributed to a gradual improvement in reported outcomes of mortality. This review provides a discussion of the cellular mechanisms and pathways involved in burn injury, resultant systemic effects on organ systems, current management and treatment, and potential therapies that we may see implemented in the future.