The introduction of oral 13-cis-retinoic acid (isotretinoin, Roaccutane/Accutane) has been a key step in he history of dermatological treatments; it was and still is more than 15 years later the only compound which cures acne while oral antibiotics and other therapies, at best, have less dramatic effects. That oral isotretinoin works so well is probably entirely linked to its effect of the sebaceous glands that dedifferentiate and stop producing sebum. Amongst oral retinoids, both natural (such an all-trans-retinoic acid and 9-cis-retinoic acid) and synthetic (such as etretinate, acitretin, arotinoids), only 13-cis-retinoic acid exerts such an effect on sebum production and therefore on acne. The cause of this specificity is still intriguing. It is likely that some pharmacokinetic properties of isotretinoin result in the specific targeting of sebaceous glands. Due to its specificity and efficacy, isotretinoin has been used for 15 years worldwide in millions of patients. Considering the broad experience gained with this drug until now, guidelines for adequate use are evolving. Accordingly, it appears appropriate to: (1) redefine the indications for treatment with oral isotretinoin; (2) reconsider cost-benefit; (3) update labeling recommendations regarding daily doses since a cumulative treatment dose appears to be accepted as a means of preventing relapse, and (4) continue to control the teratogenic risk. These questions were the 'raison d'être' of this symposium.