The management of axial spondyloarthritis includes a structured baseline assessment of the disease and follow-up of treatment efficacy using validated instruments. The treatment will depend on the severity and predominant manifestations of the disease. The cornerstone of management remains physical therapy and nonsteroidal anti-inflammatory drugs. Disease-modifying antirheumatic drugs such as sulfasalazine have shown efficacy only in treating peripheral arthritis, whereas thalidomide and pamidronate have shown some efficacy in treating axial inflammation. Anti-tumor necrosis factor-alpha agents are an efficacious option for treating signs and symptoms of axial disease, peripheral arthritis, and enthesitis, and for improving functional outcomes. They have not shown efficacy in reducing radiographic progression in axial disease. Recent evidence suggests that the new bone formation in ankylosing spondylitis may be due to upregulation of Wnt signaling in the osteoblastic pathway secondary to low serum DKK-1 levels, which are further suppressed by tumor necrosis factor inhibitor therapy.