The mechanisms underlying the sudden infant death syndrome (SIDS) appear to have origins in the fetal environment resulting in neural damage which later compromises responses to breathing or blood pressure challenges during sleep. The deficits appear to involve alterations in neurotransmitter receptors within regions involved in chemoreception and cardiovascular control. SIDS risk is enhanced by pre- and postnatal nicotine exposure, and possibly by hypoxic experiences. The prone sleeping position plays a significant role in risk, as do head positions that minimize facial escape from enclosed spaces; elevated body temperature may also be a factor. Compensatory mechanisms, including diminished gasping ability, relative failure to arouse to a safer state, or a failure to recruit respiratory efforts to overcome a blood pressure loss have been the object of recent research efforts. The findings suggest that the fatal event involves a neurally-compromised infant, circumstances that challenge vital physiology, most likely during sleep, at a particular developmental period.