This review is concerned with the effects of normal aging on the structure and function of prefrontal area 46 in the rhesus monkey (Macaca mulatta). Area 46 has complex connections with somatosensory, visual, visuomotor, motor, and limbic systems and a key role in cognition, which frequently declines with age. An important question is what alterations might account for this decline. We are nowhere near having a complete answer, but as will be shown in this review, it is now evident that there is no single underlying cause. There is no significant loss of cortical neurons and although there are a few senile plaques in rhesus monkey cortex, their frequency does not correlate with cognitive decline. However, as discussed in this review, the following do correlate with cognitive decline. Loss of white matter has been proposed to result in some disconnections between parts of the central nervous system and changes in the structure of myelin sheaths reduce conduction velocity and the timing in neuronal circuits. In addition, there are reductions in the inputs to cortical neurons, as shown by regression of dendritic trees, loss of dendritic spines and synapses, and alterations in transmitters and receptors. These factors contribute to alterations in the intrinsic and network physiological properties of cortical neurons. As more details emerge, it is to be hoped that effective interventions to retard cognitive decline can be proposed.