Undifferentiated spondyloarthritis (USpA) include incomplete forms or early phases of definite seronegative spondyloarthritis (SpA) and cases of spondyloarthritis that remain undifferentiated. The treatment of SpA is more conditioned by the disease localization. Non-steroidal anti-inflammatory drugs and disease-modifying antirheumatic drugs are the main therapeutic agents for the treatment of peripheral arthritis in USpA. Tumor necrosis factor-α (TNF-α) has been detected in sacroiliac joints of patients with SpA. Anti-TNF-α therapy has been shown efficacious in patients with active ankylosing spondylitis (AS) and psoriatic arthritis. Similar to these SpA subtypes, therapeutic options in USpA are also limited. In those cases in which severe symptoms persist despite these treatments or when there is a severe axial involvement, biologic therapy (such as anti-TNF-α agents) represent an effective choice. In these patients, anti-TNF-α treatment raises the important possibility of blocking a shift from USpA to differentiated forms of spondyloarthritis.