Treatment of a burn wound often depends on the vertical depth of injury, which is commonly determined by visual assessment. Burn progression is the concept that in the early post-burn period, a partial thickness burn may progress to a deeper burn requiring surgery. Therefore, the initial appearance of the wound may not be indicative of the eventual extent of injury. Several preclinical studies attribute burn wound progression to events such as vasoconstriction, inflammation, programmed cell death, free radical damage, and microvascular occlusion. Due to the concern for translatability of animal models for burn wounds, human studies are essential to understand burn progression in patients. Unfortunately, only a few small human studies exploring mechanisms including apoptosis, ischemia, and infection exist. Inherent to determining burn progression is burn depth determination and healing potential, an area of research that has many ongoing investigations without a clear standard method to replace visual evaluation. Treatments to prevent burn progression in humans, including use of negative pressure wound therapy and application of cooling dressings, have been studied with small sample sizes. Here, we aim to summarize the current data on human burn progression. Additionally, we discuss novel methods that could be used in future research to define early burn wound progression. Future work in human tissue should focus on the assessment and timeline of progression, explore the reversibility and prevention of injury progression and use animal models in parallel as complementary tools for hypothesis-driven research based on findings in humans.