Cutaneous manifestations of lupus erythematosus (CLE) are manifold, presenting with unspecific skin manifestations or well-defined clinical dermatological entities. Their relation to each other as well as to systemic lupus erythematosus is variable, yet diagnostically and therapeutically challenging. Therapeutic decisions have to be based on the activity and distribution as well as the type of skin lesions and the extent of systemic disease. Limited skin manifestations may be amply tackled by topical therapy, so far, mainly relying on corticosteroids. In many cases, however, internal treatment has to be combined by using antimalarials, in addition to strict UV-protection. The advent of topical calcineurin inhibitors has contributed substantially to the armamentarium of external treatment options. By specifically interfering with intracytoplasmic signal transduction to activate the nuclear factor of activated T-cells (NF-AT), they are able to modulate various inflammatory mechanisms. The two available compounds, pimecrolimus and tacrolimus, do not induce the skin atrophy characteristic of corticosteroids. They have been studied in a number of case reports, but only in a few randomized, comparative studies. Both are well-tolerated, but differentially effective in the various subsets of CLE. Further studies are needed to directly compare the two compounds to each other, as well as to topical corticosteroids, before final recommendations can be made.