Antihistamines have been classifed as first or second generation drugs, according to their pharmacokinetic properties, chemical structure and adverse effects. The adverse effects of antihistamines upon the central nervous system (CNS) depend upon their capacity to cross the blood-brain barrier (BBB) and bind to the central H1 receptors (RH1). This in turn depends on the lipophilicity of the drug molecule, its molecular weight (MW), and affinity for P-glycoprotein (P-gp) (CNS xenobiotic substances extractor protein). First generation antihistamines show scant affinity for P-gp, unlike the second generation molecules which are regarded as P-gp substrates. Histamine in the brain is implicated in many functions (waking-sleep cycle, attention, memory and learning, and the regulation of appetite), with numerous and complex interactions with different types of receptors in different brain areas. Bilastine is a new H1 antihistamine that proves to be effective in treating allergic rhinoconjunctivitis (seasonal and perennial) and urticaria. The imaging studies made, as well as the objective psychomotor tests and subjective assessment of drowsiness, indicate the absence of bilastine action upon the CNS. This fact, and the lack of interaction with benzodiazepines and alcohol, define bilastine as a clinically promising drug with a good safety profile as regards adverse effects upon the CNS.