Recently, there has been growing interest in using functional magnetic resonance imaging (fMRI) for the evaluation of psychopharmacological drugs. fMRI studies in healthy human volunteers and psychiatric patients focus on cerebral activity following acute drug administration (single challenge) and on adaptive effects on neural networks due to long-term medication. In our own fMRI studies, the effects of olanzapine or amisulpride in never treated or medication-free schizophrenic patients using robust motor, visual, and acoustic tasks was longitudinally examined. In agreement with previous reports in the literature it could be shown that, in contrast to traditional neuroleptics, atypical drugs do not decrease the activation of the sensorimotor cortex but rather normalize the reduced frontoparietal activation as well as the neuropsychological test results. This encourages the assumption that atypical antipsychotics seem to support the recovery or normalization of frontoparietal brain dysfunction in schizophrenia. However, with these new opportunities additional methodological considerations and limitations emerge.