Drugs with antihistamine action are the most commonly prescribed medication in daily dermatologic practice, both to adults and children. This article addresses new concepts of the role of histamine receptors (H1 receptors) and discusses the anti-inflammatory effects of these drugs. Second generation antihistamines differs from first generation because of their high specificity and affinity for peripheral H1-receptors. Second generation antihistamines are also less likely to produce sedation because they have less effect on the central nervous system. Although the efficacy of the various H1-antihistamines in the treatment of allergic patients is similar, even when comparing first- and second-generation drugs, these drugs are still very different in terms of their chemical structure, pharmacology and toxic properties. Consequently, knowledge of their pharmacokinetic and pharmacodynamic characteristics is essential for a better medical care, especially that offered to pregnant women, children, the elderly, and patients with comorbidities.