Objective: To analyze the clinical efficacy of anti-tumor necrosis factor-alpha (TNF-alpha) therapy in treatment of synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome, we describe cases of refractory SAPHO syndrome and review cases treated with anti-TNF-alpha reported in the literature., Methods: We describe 6 cases of patients with SAPHO syndrome treated with anti-TNF-alpha between 2004 and 2008. Therapeutic response was evaluated according to improvement in pain score, amelioration of disease activity, and improvement in function. The efficacy of treatment was considered to be reduced need for analgesics and/or antiinflammatory therapy., Results: In our series, 4 patients received infliximab, 1 etanercept, and 1 adalimumab. These treatments brought clinical response in 4 patients (66.6%): response was sustained with infliximab in 1 case for 7 months; with adalimumab in another case for 22 months; and with etanercept in 2 cases for 1 and 42 months, respectively. In contrast, 2 other patients showed no response to infliximab. Improvement was initially temporary after infusions 1 and 2, then pain recurred at Week 14. Skin lesions were healed in 3 of 4 cases, but recurred or worsened in 2 cases, after infusion 2 of infliximab. Treatment was generally well tolerated. Paradoxical psoriasis was noted in 2 cases and urticaria in 1., Conclusion: Given our results and those from the literature, TNF-alpha blockers should be considered in the therapeutic strategy of refractory cases of SAPHO syndrome, despite their effect seeming less impressive than in other spondyloarthropathies.