Adolescence is a critical period of neurodevelopment for stress and appetitive processing, as well as a time of increased vulnerability to stress and engagement in risky behaviors. This study was conducted to examine brain activation patterns during stress and favorite-food-cue experiences relative to a neutral-relaxing condition in adolescents. Functional magnetic resonance imaging was employed using individualized script-driven guided imagery to compare brain responses with such experiences in 43 adolescents. Main effects of condition and gender were found, without a significant gender-by-condition interaction. Stress imagery, relative to neutral, was associated with activation in the caudate, thalamus, left hippocampus/parahippocampal gyrus, midbrain, left superior/middle temporal gyrus, and right posterior cerebellum. Appetitive imagery of favorite food was associated with caudate, thalamus, and midbrain activation compared with the neutral-relaxing condition. To understand neural correlates of anxiety and craving, subjective (self-reported) measures of stress-induced anxiety and favorite-food-cue-induced craving were correlated with brain activity during stress and appetitive food-cue conditions, respectively. High self-reported stress-induced anxiety was associated with hypoactivity in the striatum, thalamus, hippocampus, and midbrain. Self-reported favorite-food-cue-induced craving was associated with blunted activity in cortical-striatal regions, including the right dorsal and ventral striatum, medial prefrontal cortex, motor cortex, and left anterior cingulate cortex. These findings in adolescents indicate the activation of predominantly subcortical-striatal regions in the processing of stressful and appetitive experiences and link hypoactive striatal circuits to self-reported stress-induced anxiety and cue-induced favorite-food craving. Hum Brain Mapp 34:2561–2573, 2013. © 2012 Wiley Periodicals, Inc.