Approach behavior occurs when an individual wants to get closer to a stimulus in the outside world that is viewed as rewarding. In contrast, avoidance behavior comprises actions that brings distance between the individual and a stimulus in the outside world and is often related to impending or experienced punishments, which threaten the integrity of the individual. In daily life, we are often faced with difficult decisions in which the same choice could lead to both rewarding and threatening outcomes creating an “approach-avoidance conflict.” Approach-avoidance conflict situations pose a unique challenge for comparing the value of available options because individuals must integrate information concerning the value of potential rewards and punishments, as well as the likelihood and magnitude of those potential outcomes. Human neuroimaging research has provided a wealth of information related to: (a) processing of emotional or threat-related stimuli and avoidance motivation, (b) reward processing and approach motivation, and (c) decision-making. Reward processing and decision-making research has highlighted the importance of a cortico-striatal network. In this presentation, several studies will be summarized that use self-reported experiences, behaviors, neuroimaging findings, and molecular tools to examine the approach-avoidance conflict and how one can use this information to better negotiate the tension between threat and reward.