Psoriasis is a chronic, systemic disease with features suggestive of autoimmune dysregulation. Patients with psoriasis vulgaris frequently experience systemic comorbidities, including cardiovascular and metabolic diseases, and approximately 30% develop psoriatic arthritis (PsA), which requires treatment. It is important that physicians and patients are aware of the breadth of treatment options available to treat the complete spectrum of psoriasis manifestations. This narrative review summarizes clinical information from approved systemic psoriasis therapies relevant to the treatment of PsA and related systemic pathologies. We include pivotal clinical trials of biologic therapies that are approved by the US Food and Drug Administration for psoriasis and PsA and additional studies identified from PubMed and congress abstract searches through August 21, 2019. We comment on the real-world effectiveness of traditional nonbiologic treatment options, including methotrexate, cyclosporine, acitretin, systemic corticosteroids, and nonsteroidal anti-inflammatory drugs and consider targeted synthetic and biologic disease-modifying antirheumatic drugs and their efficacy and safety in treating skin and joint manifestations. Finally, we discuss key considerations when managing patients with PsA as a comorbidity of psoriasis. The individual treatment needs of patients should be met while psoriasis and its systemic complications are managed. When addressing these needs, it is important to consider modern biologics and other systemic therapies. J Drugs Dermatol. 2020;19(3): doi:10.36849/JDD.2020.4690THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.