Topical steroids are still used suboptimally, but remain the mainstay of atopic dermatitis treatment. Topical steroid phobia is rampant in many countries, a real advantage for the entry on the market of topical immunomodulators (TIMs), which inhibit both antigen specific and non-specific T cell activation in the skin, by blockade of gene transcription of proinflammatory cytokines such as IL2 and TNF alpha. Topical tacrolimus and pimecrolimus have the most advanced clinical development. Tacrolimus, already used orally in transplantation medicine, is already available in France since 2003 as a 0.03% ointment for children (Protopic, Fujisawa). Its introduction on the market has substantially changed prescription habits in atopic dermatitis. Recalcitrant adolescent and adult head and neck lesions are the major target, but the drug is is also widely used in children, with a good safety profile. The risk of herpes virus superinfections did not increase significantly in clinical trials but needs further monitoring. Long-term prescription will need a closer look at a still much debated increased skin cancer risk. The marked efficacy on thin skin sites and absence of atrophogenic properties of the drug balance its side effects at the first applications on inflamed skin (pruritus, burning sensation). Clinical studies using pimecrolimus (Elidel, Novartis), marketed as a 1% cream, show a satisfactorily efficacy profile in adults and children including infants. The drug is better tolerated and is already widely introduced on the international market since 2002 with a pediatric positioning, but is nor available yet in 2004 in France. Besides phototherapy, systemic immunosuppressants remain useful drugs in severe disease especially in older children and adolescents, cyclosporin remaining the leading drug. Preventive immunomodulation modifying the intestinal microflora is very promising approach which deserves a large-scale assessment.