Introduction Behcet's syndrome is a chronic, multi-system, variable vasculitis of unknown etiology that can result in significant morbidity and mortality. Mucocutaneous lesions such as oral ulcers and genital ulcers are common manifestations that can affect the quality of life of patients significantly. Treatment for mucocutaneous lesions in Behcet's syndrome continues to be critical, and an unmet need remains a significant issue. Areas covered This review evaluates the mechanism of action of apremilast, its effect on the number and pain of oral ulcers, other manifestations, such as genital ulcers, disease activity, quality of life and safety profile in Behcet's syndrome patients. Data from clinical trials as well as observational studies were included. Expert opinion Two randomized placebo-controlled trials and real-world observational data suggest that apremilast is an effective and well-tolerated treatment modality for oral and genital ulcers in Behcet's syndrome. Observational studies additionally showed beneficial results for skin lesions, arthritis, and intestinal involvement.