Clobetasol propionate is the most potent of all topical steroids. It is successfully applied in the treatment of various skin diseases such as atopic dermatitis, psoriasis and vulvar lichen sclerosus. The therapy is, however, mainly symptomatic. A preventive effect is only reported in the treatment of the latter. Clobetasol propionate exerts antiinflammatory, immunosuppressive and antimitotic effects influencing the growth, differentiation and function of various cells and inhibiting cytokine production. Seven different dosage forms are available to deliver the drug to the living cells of the skin. Their choice might additionally affect patient compliance. The potency of clobetasol propionate, however, is accompanied by local and systemic side effects, such as skin atrophy and hypothalamic-pituitary-adrenal axis suppression. Patients applying clobetasol propionate must be well instructed in how to use it. Physicians prescribing clobetasol propionate should consider a diversity of factors and be able to answer the questions where, when and why.