Background: The basal ganglia, hippocampus, and thalamus are involved in the regulation of human feeding behavior. Recent studies have shown that obesity [body mass index (BMI; in kg/m2) > 30] is associated with loss of gray and white matter. Objective: It is unknown whether the subcortical brain structures that are actually involved in feeding behavior also show volume changes in obesity. Therefore, the purpose of this study was to evaluate the volumes of the basal ganglia, hippocampus, and thalamus in obesity. Design: Three-dimensional T1-weighted magnetic resonance imaging scans of the brain were analyzed by using automatic segmentation to measure volumes of the nucleus accumbens, globus pallidus, amygdala, putamen, caudate nucleus, thalamus, and hippocampus in 471 subjects (mean age: 74.4 y; 56% men). Results: Obese subjects had larger left (P = 0.013) and right (P = 0.003) amygdalar volumes and a larger left hippocampal volume (P = 0.040) than did normal-weight subjects (BMI < 25). None of the other subcortical structures differed in size between these groups. After correction for age, sex, smoking, hypertension, and pravastatin use, BMI was associated with left (β = 0.175, P = 0.001) and right (β = 0.157, P = 0.001) amygdalar volumes and with left hippocampal volume (β = 0.121, P = 0.016). Conclusions: This study showed that the amygdala and hippocampus are enlarged in obesity. In consideration of the function of these structures, this finding may indicate that hedonic memories could be of major importance in the regulation of feeding. Because of the cross-sectional design, cause and effect could not be discriminated in this study.