Historical progress in medicine can be charted along the lines of technical innovations that have visualized the invisible. One hundred years ago, Alois Alzheimer exploited newly developed histological stains to visualize his eponymonous disease in dead tissue under the microscope. Now, as we are entering the second century of Alzheimers disease research, technical innovation has endowed us with a range of in vivo imaging techniques that promise to visualize Alzheimer disease in living people. The earliest stage of Alzheimers disease is characterized by cell-sickness, not cell-death, and can occur before the deposition of amyloid plaques or neurofibrillary tangles. In principle, functional imaging techniques might be able to detect this early stage of the disease, a stage that was invisible to Alzheimer himself. Here, we will first define the neurobiological meaning of function and then review the different approaches that measure brain dysfunction in Alzheimer disease.