Background: Psoriasis patients carry an increased risk for associated comorbidities. Dermatologists have to be aware of the effects of systemic treatments not only on psoriasis but also on co-occurring diseases. In case of other coexisting inflammatory diseases, the right psoriasis treatment may improve both disorders. For infectious and malignant disorders, some treatments have to be avoided as they may be harmful. Objective: The primary objective of this project 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 eight psoriasis experts. Results: Recommendations are given on the use of systemic treatment in psoriatic arthritis, inflammatory bowel disease, demyelinating disorders, hepatitis B and C, HIV and cancer. Conclusion: This expert opinion is a practical guide for dermatologists when handling psoriasis patients with these specific conditions.