Normal aging, in the absence of neurodegenerative disease, can provide important insights into the mechanisms by which the brain can maintain cognitive abilities across the lifespan. Hippocampal-dependent memory processes can become vulnerable as age advances. The focus of this chapter is the contribution of hippocampal granule cells to cognitive impairments that are observed during aging. A number of alterations in structure, function, and gene expression have been observed in aged granule cells, any of which may lead to adaptive, compensatory or detrimental consequences to hippocampal function. As the average life span of humans continues to increase, those who reach 100 years or beyond is more common. Individuals that have aged successfully, and exhibit high levels of cognitive ability can provide useful clues into the enormous potential possessed by the mammalian brain.