With advances in human structural and functional neuroimaging, 21st Century neuropsychology has been provided myriad opportunities to expand its ‘neuro’ purview. The opportunities span research and clinical fronts but come with the responsibility of the user to understand the complexities, scope, and limits of imaging modalities employed. The purpose of this special issue of Neuropsychology Review is to provide didactic descriptions of commonly used imaging modalities and instances of how each modality has supported and expanded concepts of neuropsychology, potentially enabling identification of mechanisms of neuropsychological observations. Also considered is the place and potential of neuroinformatics in managing and making useful the vast datasets generated with neuroimaging methods combined with neuropsychological testing. The reviews present a sampling of 21st century imaging approaches and informatics considerations for identifying the “neuro” in neuropsychology.