We report the usage of the TNF-alpha antagonist adalimumab in patients with progressive multisystem sarcoidosis. Three patients with multisystem sarcoidosis (MSS) were treated with adalimumab for 12 months. All three patients were quickly responded to adalimumab and experienced a nearly complete regression of the symptoms that lead to an intensive immunosuppression. However, some accompanying symptoms of sarcoidosis, such as splenomegalia, did not respond. One patient suffered 18 months later a new unspecified abdominal lymphadenopathy. TNF-alpha antagonists can be helpful agents in the treatment for MSS. However, the experience with TNF-alpha antagonists in patients with sarcoidosis is still limited. Multicenter trials and a comparison of the different agents are needed to validate the safety and efficacy in these patients. Optimal dosage, duration of therapy and long-term toxicity of anti-TNF therapy in patients with refractory sarcoidosis are yet to be determined in prospective trials.