Intramedullary nailing is the preferred treatment method for stabilizing femoral diaphyseal fractures. Despite its superior biomechanical advantages over other implants, its use, particularly in selected groups of patients, has been questioned because of the possible harmful systemic effects of intramedullary reaming. The increase in intramedullary canal pressure during intramedullary nailing can result in intravasation of bone marrow and fat into the venous blood system. The subsequent consequences can be fat embolism syndrome (FES), adult respiratory distress syndrome (ARDS), and multiple organ failure. The lung seems to be the primary target for fat embolization and for the mediated effects primed by inflammatory reactions. In laboratory studies, both reamed and unreamed intramedullary nailing has been shown to alter selected pulmonary variables. Although transient, this effect appears to be more prominent with reamed than unreamed techniques. Additional studies are required to determine whether a subgroup of trauma patients is adversely affected by intramedullary reaming, thus necessitating other fixation techniques.