Operative smoke alarms have been shown to be effective in reducing home-fire fatalities, but there remain incidents in which injuries and death occur despite the presence of a working smoke alarm. The present work presents a scientifically-guided framework for evaluating the outcomes of such incidents from the perspective of human factors and, specifically, the warnings communication process. It considers the roles of environmental, individual, and situational factors in occupants’ detection, noticing, and processing of smoke alarms, as well as the behaviors produced in response. Such factors include the acoustic environment in which the alarm sounds, the occupants’ cognitive state and focus of attention, the occupants’ developmental and physical abilities, and the situational circumstances in which a response is chosen and executed. The synthesis of these findings provides one methodology for understanding real-world outcomes of fires, as well as informing development and evaluation of countermeasures for improving residential fire fatality rates.