Functional brain imaging has overshadowed traditional lesion studies in becoming the dominant approach to the study of brain-behavior relationships. The proponents of functional imaging studies frequently argue that this approach provides an advantage over lesion studies by observing normal brain activity in vivo without the disruptive effects of brain damage. However, the enthusiastic onslaught of brain images, frequently presented as veridical representations of mental function, has sometimes overwhelmed some basic facts about brain organization repeatedly observed over more than a century. In particular, the lateralization of speech and language to the left cerebral hemisphere in over 90% of the right-handed population does not appear to have been taken as a serious constraint in the interpretation of imaging results in studies of these functions. This paper reviews a number of areas in which standard activation assumptions yield results that are at odds with clinical experience. The activation approach will be contrasted with a performance-based analysis of functional image data, which, at least in the case of speech production, yields results in better agreement with lesion data. Functional imaging represents enormous opportunities for understanding brain-behavior relationships, but at the present level of understanding of what is being represented in such images, it is premature to adhere to a single approach based on the strong but questionable assumptions inherent in most activation studies.