AbstractFunctional MRI (fMRI) has become the most widely used modality for examining human brain function in basic and clinical neuroscience. As compared to the application of fMRI in basic neuroscience research, clinical fMRI presents unique challenges. A growing body of literature supports the feasibility of clinical fMRI, with the best‐studied applications being localization of motor cortex and lateralization of language. While it may be tempting to assume that fMRI will supercede prior approaches, it may turn out that fMRI will be used to complement more difficult or invasive methods rather than replace them entirely. This article focuses on fMRI studies in patients and patient populations. Specific considerations for such applications include pathophysiological effects on functional physiology, brain–behavior correlations in the presence of cognitive or sensorimotor deficits, and test‐retest reliability for longitudinal studies. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.