Atopic dermatitis (AD) is a chronic, relapsing, highly pruritic inflammatory skin disease that is particularly prevalent in the paediatric population. Emollients and topical corticosteroids have represented the standard of treatment for patients with AD, despite their numerous adverse effects and patients' tendency towards steroid resistance. Topical tacrolimus marks the introduction of an entirely new class of medications, the non-corticosteroid topical immunomodulators. Numerous short- and long-term and ongoing paediatric and adult studies have demonstrated the excellent efficacy and superb safety profile of this anti-inflammatory agent. The authors review many of these landmark studies and discuss the mechanism of action and safety profile of tacrolimus, in the context of the pathophysiology of AD.