Significant structural trimming of neuronal structures in the cerebral cortex has long been considered as a primary cause of various age-related cortical dysfunctions. While recent findings provided additional data to support this notion, current understanding of cortical neuronal functions in aging also revealed the relationship of neuronal plasticity and imbalances between different neurotransmitter systems with the formation of age-related cortical dysfunctions. Manipulating these age-related alterations in neuronal function may be a novel therapeutic approach in the treatment of cortical dysfunctions in aging. This review will focus our current understanding of age-related changes in neuronal structures and functions in the cerebral cortex. Implication of these age-related alterations will be discussed.