Major thermal injury induces the activation of an inflammatory cascade that contributes to the development of subsequent immunosuppression, increased susceptibility to sepsis and multiple organ failure. The productive capacity of macrophages for inflammatory mediators, (i.e., nitric oxide, prostaglandins, TNF-alpha, IL-6 etc.), is profoundly increased post-burn, thereby implicating macrophages in the development of the post-burn immunosuppression. This review will focus on recent findings with regards to the role of macrophages in the development of post-burn immunosuppression with particular emphasis on the role of nitric oxide and prostaglandins.