Accurate appraisal of meaningful environmental signals involves the interpretation of salient information for their intrinsic emotional value and personal relevance. We examined the neural basis for these components of endogenous salience during such appraisals using trial-related functional magnetic resonance imaging (fMRI). Subjects viewed affective pictures and assessed either the emotional intensity or extent of self-relatedness of the content of those pictures. In a parametric factorial design, individualized subjective ratings of these two dimensions were correlated with brain activity. The nucleus accumbens (NAcc) responded to both increasing emotional intensity and self-relatedness. Activity in the amygdala was specifically related to affective judgments and emotional intensity. The volitional act of appraising the extent of personal association specifically engaged the ventral medial prefrontal cortex (MPFC), and additionally recruited dorsal medial frontal regions and insula as the extent of self-relatedness increased. The findings highlight both overlapping and segregated neural representations of intrinsic value and personal relevance during the appraisal of emotional stimuli.