Ankylosing spondylitis (AS) is a chronic and progressive inflammatory disorder that primarily affects the axial skeleton. Unfortunately, diagnosis of AS is often delayed compared to other rheumatologic conditions. It is not uncommon for patients to already have an advanced disease when the correct diagnosis is eventually made. TNF inhibitors are well-known and effective treatment options in patients with AS. However, many clinical trials have excluded patients with advanced AS. This paper reports a 45-year-old male with newly diagnosed AS with already fused sacroiliac joints, lumbar spine, and cervical spine. Due to persistent and severe pain despite having taken multiple NSAIDs, etanercept was prescribed. After 4 years of treatment, the patient continues to experience marked improvement of his AS symptoms without any significant adverse effects. This case illustrates etanercept can be an effective treatment in patients with advanced AS and is well tolerated. An extensive literature review is also carried out regarding this topic.