Hematopoietic stem cell transplantation (HSCT) is a therapeutic option for a number of malignant and inherited disorders. However, the efficacy of this therapy is limited by a number of serious infectious and noninfectious complications. Pulmonary infections represent a significant cause of morbidity and mortality post-HSCT and can occur both pre- and post-hematopoietic reconstitution. Susceptibility to Gram-negative bacterial infections despite full hematopoietic engraftment suggests that innate immunity remains impaired months to years post-HSCT. This review will describe the process and complications of HSCT and will summarize what is known about innate immune reconstitution post-HSCT. Data from the literature as well as our own laboratory will be presented to suggest that an eicosanoid imbalance characterized by over-production of prostaglandins and under-production of leukotrienes leads to impaired lung phagocyte function post-HSCT. Of therapeutic interest, strategies which limit production of prostaglandins can improve pulmonary host defense in animal HSCT models, which suggests that this may also be beneficial for human HSCT recipients.