Background: There is limited information on systemic and biological treatment optimization and transitioning in routine clinical practice. Objective: To provide practical guidance on treatment optimization and transitioning for moderate-to-severe plaque psoriasis. Methods: Dermatologists from 33 countries contributed to the Transitioning Therapies programme. Fourteen questions were identified. Answers were drafted based on systematic literature reviews (7/14 questions) and expert opinion (7/14 questions). Using a modified Delphi procedure, dermatologists from 30 countries voted on their level of agreement with each draft answer (scale: 1-9, strong disagreement to strong agreement). Consensus was defined as ≥75% of participants scoring within the 7-9 range. Results: Consensus was achieved on the answers to all questions. Recommendations for the use of cyclosporine and methotrexate were agreed. Transitioning from a conventional systemic therapy to a biological agent may be done directly or with an overlap (if transitioning is required because of lack of efficacy) or potentially with a treatment-free interval (if transitioning is required for safety reasons). Combination therapy may be beneficial. Continuous therapy for patients on biologicals is strongly recommended. However, during successful maintenance with biological monotherapy, a dosage reduction may be considered to limit drug exposure, although this may carry the risk of decreased efficacy. Switching biologicals for reasons of efficacy should be done without a washout period, but switching for reasons of safety may require a treatment-free interval. Conclusion: This consensus provides practical guidance on treatment optimization and transitioning for moderate-to-severe plaque psoriasis, based on literature reviews and the expert opinion of dermatologists from across the globe. © 2013 European Academy of Dermatology and Venereology.