Histamine determines a variety of physiologic and pathologic responses in different tissues and cells and it is an important chemical mediator on inflammation in allergic disease. Therefore the H1-receptor antagonist are among the most widely used medications in the world. We review here the molecular basis of their action and their clinical pharmacology, efficacy in allergic disorders and adverse reaction with a particular attention in children. We will also underline the different role of first generation H1-receptor, relatively sedating, and the second generation H1-receptor antagonist, relatively non-sedating.