Exposure to asphyxiant gases is a ubiquitous feature of the fire environment, particularly in structural (or closed-space) fires. The clinician evaluating the smoke-inhalation patient must keep in mind the manifold actions of systemic toxicants upon an individual whose pulmonary gas exchange may be compromised and whose circulatory and metabolic status may be stressed by burns, hypo- or hypervolemia, and intercurrent disease. Also to be considered is the likelihood of exposure to multiple toxicants whose physiologic effects may be synergistic and whose therapeutic demands may be conflicting. As newer therapeutic regimens and rapid laboratory tests become available, the clinician should be prepared to evaluate their strengths and limitations for the complex task of evaluating and treating smoke-inhalation patients.