Choline participates in several relevant neurochemical processes. It is the precursor and metabolite of acetylcholine (ACh), plays a role in single-carbon metabolism and is an essential component of different membrane phospholipids (PLs). PLs are structural components of cell membranes involved in intraneuronal signal transduction. This paper reviews the roles of choline and of choline-containing phospholipids (CCPLs) on brain metabolism in health and disease followed by an analysis of the effects of exogenously administered CCPLs on the brain, a topic extensively investigated by literature. Based on the observation of decreased cholinergic neurotransmission in brain disorders characterized by cognitive impairment, cholinergic precursor loading therapy with CCPLs was the first approach used to attempt for relieving the cognitive symptoms of Alzheimer's disease. This therapeutic strategy was discontinued due to the negative clinical results obtained with choline or lecithin. Negative results obtained with some compounds cannot be generalized for all CCPLs, as CDP-choline (citicoline) and to a greater extent choline alphoscerate (GPC) displayed interesting effects documented in preclinical studies and limited clinical trials. We provide evidence in favor of CDP-choline and GPC activity in cerebrovascular or neurodegenerative disorders characterized by cholinergic neurotransmission impairment. Based on the results of the controlled clinical trials available, we suggest that due to the lack of novel therapeutic strategies, safe compounds developed a long time ago such as effective CCPLs could have still a place in pharmacotherapy. Therefore selected compounds of this class should be further investigated by new appropriate clinical studies.