The mammalian brain has an exceptional ability to associate aversive and rewarding stimuli with environmental cues. The correct discrimination between harmful and beneficial stimuli allows an organism to select the most appropriate response, thereby protecting it from danger. In humans, inappropriate retrieval of reward associated memories is the framework for substance abuse, whereas inappropriate retrieval of fear/aversive memories can lead to the development of anxiety disorders. Understanding the neural circuits mediating the integration of fear- and reward-associated memories may uncover more effective therapies for patients suffering from both anxiety and substance-related addictive disorders.