Neurodegenerative processes are one of the main age-related features of dogs. Senile neurodegeneration can be clinically asymptomatic, “borderline” (i.e., a condition that is intermediate between normal and disease state) or progress toward overt clinical abnormalities, known as age-related cognitive disorders, cognitive dysfunction syndrome (CDS), or senile dementia. The aim of the present article is to review the rationale for the use of phosphatidylserine (PS), a natural phospholipid, in the management of brain neurodegenerative processes in senior dogs. The preliminary clinical data on PS supplementation in senior dogs will also be reviewed. There is evidence that PS is absorbed rapidly, reaches high concentrations in the brain, and is well tolerated. Phosphatidylserine has emerged to exert several in vitro and in vivo neuroprotective activities. It has been shown to positively affect neurotransmitter release and neurotransmitter receptor density in several brain regions from laboratory animals with memory impairments. Phosphatidylserine also was found to revert experimentally-induced amnesia in rats and improve memory deficits both in old animals and in elderly humans with various degrees of cognitive impairment and Alzheimer's dementia. On the basis of the data reported in the scientific literature, PS stands out as an essential “brain nutrient.” In view of these features, some supplements containing PS have been licensed recently as adjuvant treatment for canine and feline brain aging. The results of the studies on its use in the preventative and combined treatment of dogs with clinical features consistent with the diagnosis of CDS are reported. Although PS-based neuroprotection in dogs and cats is still at its infancy, the preliminary collected data look promising and thus merit further investigation.