Understanding the cellular mechanisms that characterize the functional changes of the aged brain is an ongoing and formidable challenge for the neuroscience community. Evidence now links changes in Ca(2+) influx and homeostasis with perturbations induced by the aging process in the function of the main intracellular organelles involved in Ca(2+) regulation: the endoplasmic reticulum and mitochondria. New perspectives are also offered by recent gene microarray studies, illustrating the multifactorial nature of the aging process.