Abstract Background Impressive progress in new therapeutic options has been made for psoriasis. Treatments include topical steroids, phototherapy, conventional, synthetic disease‐modifying drugs and an expanding list of biologics. Objective The primary objective of this work was to collect evidence for the creation of practice guidelines for systemic treatment of psoriasis (BETA‐PSO: Belgian Evidence‐based Treatment Advice in Psoriasis). Methods Evidence‐based recommendations were formulated using a quasi‐Delphi methodology after a systematic search of the literature and a consensus procedure involving 8 psoriasis experts. Results In this part, the use of systemic treatment in different age groups, during pregnancy, in metabolic syndrome, in patients with mental health problems, in different psoriasis subtypes and in previously systemically treated patients treatment is discussed. Conclusion Guidance on therapeutic choice in specific clinical situations in psoriasis is provided in order to facilitate the decision‐making in clinical practice.