AS is the prototypical member of the family of spondyloarthropathies, and is characterized by seronegativity, axial predominance and new bone formation, which underlie symptoms of inflammatory back pain, enthesopathy and extra-articular manifestations, including anterior uveitis, psoriasis and colitis. Patients with AS typically experience a wide variety of morbidities. These include both morbidities related to the disease itself—most prominently progressive, irreversible, structural damage to the axial or peripheral skeleton—and morbidities stemming from treatments for the disease, including toxicities from NSAID use, and increased risk of infections and immunogenicity concerns with biologics. AS is also associated with a number of comorbidities. We review the risks associated with AS, its comorbidities and its treatments, as well as strategies that can be used to mitigate these risks in patients with AS.