Recently, the National Institute on Aging (NIA) and the Alzheimer’s Association (AA), identified specific structural and functional neuroimaging findings as valuable markers of biological processes occurring in the human brain -- especially, processes that herald impending dementia due to Alzheimer’s disease (AD), in its prodromal form. In particular, the imaging modalities of MRI and PET were singled out, along with certain biomarkers in cerebrospinal fluid (CSF), to serve this purpose. We review the clinical tests available for neuropsychologic evaluation and in cases when the differential diagnosis for the causes of cognitive impairment is difficult to make, we consider biomarkers, beginning with CSF, for assessment of cognitive decline. For more direct information about dementia-related pathologic changes in brain tissue, structural features observed in MRI scans are regarded. We next discuss the use of SPECT for evaluating functional changes. Then, pertinent to the recent NIA/AA consensus statement on the diagnosis of prodromal AD, we focus upon assessing the cerebral metabolic changes associated with neurodegenerative diseases that are identified with FDG-PET, as well as consider the most appropriate roles for amyloid imaging based upon recent studies examining the use of PET with tracers having higher retention in brain tissue harboring plaques comprised of insoluble beta-amyloid. We also consider leading causes for the current underutilization of neuronuclear imaging in evaluating patients with cognitive problems, along with strategies for combating them. Finally, we suggest an overall diagnostic algorithm to guide optimal use of all the neuroimaging tools in assessing patients with cognitive decline.