For the past 60 years of burn therapy in China, the incidence of infection declined gradually, however, the drug-resistant pathogens have become increasingly serious. From the research of the enterogenous infection to the wound coverage by allograft skin, from the endotoxin and exotoxin-targeted therapy of pathogens to empirical usage of antibiotics, these efforts had established the first line of barrier against pathogens and reduced the incidence of sepsis obviously. Recently, many studies have been carried out to investigate the regulatory mechanism underlying the host immunity in defending the pathogens and controlling the excessive inflammation after major burns. The resulting strategies of immunomodulation of burn infection by Chinese and western medicine were contributed to the second immune barrier against the invaded pathogens. With the updated medical technology to treat the infection both symptomatically and etiologically, the incidence and severity of infection were reduced remarkably. In the future, further studies should be focus on applying the new technology to detect the pathogenic microorganism quickly, finding the novel biomarkers for evaluation of immune status, and following up the long-term impact of infection on host immunity in extensively burn patients.