Ankylosing spondylitis (AS) is associated with several comorbidities which contribute significantly to morbidity and mortality and add to the complexity of management. In addition to the well known extra-articular manifestations and increased cardiovascular risk, several pulmonary, renal, and neurological complications which have been associated with AS deserve equal attention. Whereas a clear link has been established for some manifestations, the evidence for other associations is less clear. Interstitial lung disease, apical fibrosis, secondary infection, and ventilatory restriction from reduced chest wall movement are well known pulmonary complications; more recently an association with sleep apnoea has been suggested. Renal amyloidosis and IgA nephropathy remain a treatment challenge which may respond to anti-TNF therapy. Atlanto axial subluxation and vertebral fractures can result in serious neurological complications and are notoriously difficult to diagnose unless a high level of suspicion is maintained. Despite several reports linking AS with demyelination a true link remains to be proved. This review discusses the prevalence, pathophysiology, and management of pulmonary, renal, and neurological complications, and implications for clinical practice.