In autoinflammatory disorders, dysregulation of the innate immune response leads to an excessive cytokine release. The disease course is often characterized by high morbidity and mortality, treatment is mostly difficult and therapeutic options are limited. In most cases, life-long control of ongoing inflammation is necessary in order to improve clinical symptoms and prevent development of damage. Steroids are helpful in many conditions, but the development of serious side effects often limits their long-term use. Other immunosuppressive, steroid-sparing medications are less effective than in the treatment of autoimmune diseases or do not show any effect. So far, anti-IL1α and/or β-blocking agents as well as an IL-6 receptor-blocking monoclonal antibody and, to a lesser extent, TNF-α blocking agents were applied in autoinflammatory disorders and significantly improved the outcome. Although these progresses were made in the last years, there are still numerous challenges in order to improve drug therapy in autoinflammation. This review summarizes the current state of new drug development and discusses advantages and disadvantages of possible targets.