Ankylosing spondylitis (AS) is a chronic inflammatory arthritis that affects the axial skeleton, causing intense pain, progressive joint destruction, and a gradual reduction in physical function. It has been recognized not only as affecting the axial skeleton but as a systemic disease. Since it also causes an increase in the rates of inflammatory bowel disease, psoriasis, acute anterior uveitis, and mental disorders affecting the quality of life. Furthermore, an association with neurological and cardiovascular events is documented. With the advent of biologics, treating AS dramatically changed due to its high efficacy and tolerable safety. AS can be treated with various biological treatments. Nevertheless, there are differences in traits, including rapidity of onset, long-term efficacy, safety profile, and influence on comorbidities. A better understanding of such traits enables clinicians to make the best decision for each patient, increasing persistence, extending medication survival, enhancing patient satisfaction, and reducing the disease effect of ankylosing spondylitis. In this article, we emphasize biologics' efficacy and safety profile in patients with ankylosing spondylitis. In addition, we discuss the impact of biologics on comorbidities and health-related quality of life.