In keeping with other studies of adolescent and adult depression, Tao et al. report that only 60% of the adolescents responded to treatment. However, they do not report whether any baseline imaging parameters predicted response relative to nonresponse, a high demand in the field. This study follows only one previous imaging plus treatment study of adolescent depression, which examined reward-related brain functioning in adolescents with depression before (but not after) treatment with either cognitive-behavioral therapy (CBT) (N=7) or CBT plus a selective serotonin reuptake inhibitor (N=6) (6). Greater striatal activity during reward outcome predicted higher general symptom severity after treatment, whereas greater striatal activation during reward anticipation predicted lower anxiety after treatment (because of the small sample size, the reported results were not specific to treatment type) (6). Results from a larger body of research in adult depression suggest a general pattern: increased baseline resting metabolism or activity in the pregenual anterior cingulate cortex (Brodmann's area 24) in response to tasks predicts responsiveness to treatment (medication) (7, 8), but increased resting metabolism or activation in the subgenual anterior cingulate cortex (Brodmann's area 25) predicts treatment resistance (medication, CBT) (9, 10). Consideration of these adolescent and adult studies highlights several points. First, fMRI strategies yield differential results, depending on the neural systems they are designed to test (e.g., resting state, threat, mood, reward). Studies that examine multiple systems may be most helpful. Second, imaging plus treatment studies will ideally address both treatment predictors and neural changes that result from treatment simultaneously. Third, larger sample sizes will be needed to delineate the effects on the brain by different types of treatment and to define differences between responders and nonresponders across treatments and age groups.