In the first part of the review, topical agents and first-line systemic treatment options for cutaneous lupus erythematosus were discussed whereas in the second part, recent information on efficacy, dosage, and side effects for further systemic treatment options are described in detail. In contrast to other immunosuppressive agents, such as azathioprine, cyclophosphamide, and cyclosporine, methotrexate has recently received more attention in the treatment of the disease. Further second-line treatment includes retinoids, dapsone, and mycophenolate mofetil. Because of severe side effects or high costs, other agents, such as thalidomide or high-dose intravenous immunoglobulins, are reserved for severe recalcitrant CLE. Biologics, ie, rituximab, have been used to treat systemic lupus erythematosus; however, in CLE, most biologics have only been applied in single cases. In addition to successful treatment, induction of CLE subtypes by biologics has been reported. In conclusion, many treatment options exist for CLE, but not many are supported by evidence from randomized controlled trials.