Although the barrier function and thickness of the stratum corneum is fully developed in newborns, the infant shows numerous differences in cutaneous and systemic metabolism of topically applied substances in comparison to adults. This discrepancy between children and adults has been explained by the greater systemic availability due to the greater surface area to weight ratio in children. Several topically applied drugs such as hexachlorophene, phenol, salicylic acid and boric acid in high concentration or on large areas have caused toxic reactions and fatalities in infants. Therapeutic approaches to childhood dermatoses differ from these used in adults. These age-dependent differences concerning the topical application of glucocorticosteroids, urea and dyes are described for the treatment of atopic eczema. The development of innovative topical drugs may extend therapeutic options especially in children as shown by a new topical anesthetic cream improving the treatment of mollusca contagiosa, a common childhood problem. Finally, certain physiological differences should be considered in newborn and infant skin care.