Simple Summary: Psoriasis is a chronic multisystem inflammatory disease associated with a wide range of comorbidities including cardiovascular disease, hypertension, diabetes, hyperlipidemia, obesity, metabolic syndrome, anxiety, depression, chronic kidney disease, and malignancy. Currently available novel therapeutic options for moderate-severe psoriasis include tumor necrosis factor alpha inhibitors, inhibitors of the interleukin 17, and inhibitors of the interleukin 23. Apart from the concomitant diseases psoriasis patients may have, biologic therapy may cause significant complications requiring close collaboration between dermatologists and physicians of different specialties. Consequently, it was our main purpose to provide an overview of each class of biologic agents, as well as of the most frequent adverse events they may cause in psoriasis patients with concomitant diseases. Psoriasis is a chronic multisystem inflammatory disease associated with a plethora of comorbidities including metabolic syndrome, cardiovascular disease, hypertension, diabetes, hyperlipidemia, obesity, anxiety, depression, chronic kidney disease, and malignancy. Advancement in unveiling new key elements in the pathophysiology of psoriasis led to significant progress in the development of biologic agents which target different signaling pathways and cytokines involved in the inflammatory cascade responsible for the clinical manifestations found in psoriasis. Currently available novel therapeutic options for moderate-severe psoriasis include tumor necrosis factor alpha inhibitors, inhibitors of the interleukin 17, and inhibitors of the interleukin 23. Nevertheless, concerns have been raised with respect to the possible risks associated with the use of biologic therapy requiring close collaboration between dermatologists and physicians of different specialties. Our aim was to perform an in-depth literature review and discuss the potential risks associated with biologic therapy in patients with psoriasis and concurrent diseases with a focus on the influence of novel therapeutic agents on liver function in the context of hepatopathies, particularly viral hepatitis. A multidisciplinary teamwork and periodic evaluation of psoriasis patients under biologic therapy is highly encouraged to obtain an accurate management for each case. [ABSTRACT FROM AUTHOR]