It is currently believed that babies die suddenly and unexpectedly during sleep when they fail to respond appropriately to a life-threatening challenge. The major risk factors, including sleeping prone, head covering, exposure to cigarette smoke, and preterm birth, all impair cardiorespiratory control and depress arousal responses from sleep. Conversely, those factors that reduce the risk, including breastfeeding, immunization, and pacifier use, increase these protective responses. Understanding the physiological mechanisms that likely underpin risk and protective factors is important so that parents and clinicians are aware that safe sleeping messages are supported by sound physiological evidence.