Psoriasis is an immune-mediated, chronic inflammatory skin disease, which is currently regarded as a systemic process given its association with multiple comorbid conditions. In psoriasis, there is a complex interaction between T cells and keratinocytes. The pathogenesis of psoriasis is not fully understood, but the IL-23/Th17 pathway is known to play the key role in the development of the disease. With the advent of genetically engineered biological drugs (GEBD), the treatment of psoriasis has undergone significant changes due to their high efficacy through targeted effects. Guselkumab is the first drug for the treatment of moderate to severe psoriasis to target the p19 subunit of interleukin (IL) 23. The efficacy of guselkumab has been demonstrated in a number of clinical trials. To date, only a few case studies from actual clinical practice have been published in the literature reflecting the use of guselkumab in severe psoriasis, including long-term drug survival and continued efficacy in patients with comorbidities. The article reviews the results of key efficacy studies of guselkumab and presents its own clinical case studies of successful use of the drug. It is noted that guselkumab is able to replicate the results obtained in studies in real clinical practice. However, the cases presented are also of interest in view of their concomitant metabolic syndrome, obesity, which often makes it difficult to respond to therapy. This group of patients is usually characterised by a particularly torpid course of psoriasis and a certain refractoriness to the ongoing treatment. Thus, guselkumab has an effective and safe profile, in addition it is convenient to use, and the improvement in the quality of life of patients during therapy makes it promising as a first-line GEBD therapy in the treatment of psoriasis. © 2022, Remedium Group Ltd. All rights reserved.