Addictions, both substance and behavioral, have been conceptualized as involving similar biopsychosocial processes with different opportunistic expressions. A maladaptive stress response in combination with craving or urges to engage in the addictive behavior may be among the underlying factors common to behavioral and substance addictions. The current study compared the neuroendocrine (cortisol) and subjective responses to stress of gamblers and smokers to healthy controls. We assessed if participants responded differently to smoking or gambling cues before and after a psychosocial stressor. To this end, the subjective urges/cravings of all participants were measured in response to smoking or gambling cues versus neutral cues, once under normal conditions and again after exposure to a stressor. Salivary cortisol was measured prior to, immediately following, and 10 minutes after conclusion of the stressor. Smokers and gamblers showed a similar blunted cortisol response to the acute stressor that differed from the control group's response. Following a stressor, subjective craving in smokers increased whereas gamblers' urges decreased. In smokers, a blunted cortisol and subjective stress response were related to increased urges. In contrast, for gamblers, changes in cortisol levels were unrelated to urges, and higher subjective stress was associated with decreased urges. In conclusion, individuals with a substance and a behavioral addiction share common patterns of reactivity to stress. However, while the stressor enhanced cue-related craving in smokers, it generally had the opposite effect on gamblers. Further research is necessary to elucidate the complicated patterns of similarities and differences that underlie substance and behavioral addictions.