Burn injuries have a consistently high rate of mortality and morbidity and will remain a major health problem because burn injuries can result in repeat admissions for reconstruction and rehabilitation. Thus, addressing the pathophysiology of burns is crucial to improve both therapeutic interventions and patient care. A number of experimental burn models have been employed to study the systemic response of the whole organism and the more detailed cellular and molecular pathways affected by burns. However, an in-depth understanding and the useful application of experimental models are essential for effectively translating laboratory outcomes to clinical treatments. This review highlights the strengths and limitations of recent experimental burn models in vivo and in vitro.