Cognitive reappraisal has been associated with increased activation in prefrontal cortex (PFC) and cingulate regions implicated in cognitive control and affect regulation. To date, neuroimaging studies of reappraisal have primarily used emotionally evocative scenes, and it remains unclear whether the same cognitive strategy applied to emotional facial expressions would involve similar or different neural underpinnings. The present study used fMRI to examine brain activation during cognitive reappraisal of negatively valenced facial expressions relative to passive viewing of negative and neutral facial expressions. Twenty-two healthy adults completed a cognitive reappraisal task comprised of three different conditions (Look-Neutral, Maintain-Negative, Reappraise-Negative). Results indicated that reappraisal was associated with a decrease in negative affect and engagement of PFC brain regions implicated in cognitive control and affect regulation (DLPFC, mPFC, and VLPFC). Furthermore, individual differences in habitual reappraisal use were associated with greater DLPFC and mPFC activation, while suppression use was associated with greater amygdala activation. The present study provides preliminary evidence that facial expressions are effective alternative 'targets' of prefrontal engagement during cognitive reappraisal. These findings are particularly relevant for future research probing the neural bases of emotion regulation in populations for whom aversive scenes may be less appropriate (e.g., children) and illnesses in which aberrant responses to social signals of threat and negative feedback are cardinal phenotypes.