SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteitis) is a rare chronic inflammatory musculoskeletal disorder of unknown etiology observed in children and young adults, which involves both osteo-articular inflammation and skin abnormalities. We review the case of a 22-year-old male, who presented with a 5-year history of hidradenitis suppurativa (HS), acne vulgaris, joint stiffness, and pain. Previous ineffective treatments included isotretinoin and oral antibiotics. Marked improvement of all cutaneous features was noticed after the first dose of infliximab and methotrexate; continued treatment resulted in the complete remission of the arthritis and enthesopathy. This case report demonstrates the efficacy and safety of infliximab and methotrexate in refractory SAPHO syndrome.