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Behçet’s disease (BD) is a multisystemic inflammatory disorder in which treatment decisions are largely driven by the pattern and severity of organ involvement. This review provides a practical, organ-based overview of current therapeutic strategies for severe and refractory BD, with an emphasis on treatment selection and timing in routine clinical practice. Recent evidence supports an upfront, intensive treatment approach for life-threatening or damage-prone organ involvement, particularly neurological, vascular, and ocular disease, where delays in inflammation control are closely associated with irreversible damage. Anti–tumour necrosis factor agents form the core of therapy in these settings, supported by the strongest disease-specific data, while other biologic and targeted therapies are increasingly used in refractory cases. In contrast, mucocutaneous and articular manifestations predominantly affect quality of life and are commonly managed with stepwise strategies. Colchicine remains a widely used first-line treatment in routine practice and provides effective control of mucocutaneous and joint manifestations in a substantial proportion of patients, with escalation to additional systemic or targeted therapies guided by persistence, refractoriness, and patient burden. Importantly, treatment responses vary across organ systems, and benefit in one domain cannot be assumed to translate to others, reinforcing the need for organ-specific treatment planning. Optimal management of BD depends on matching treatment intensity to organ-specific risk, prioritising early aggressive therapy for major organ involvement while adopting proportionate, stepwise approaches for non–life-threatening disease. Improved outcomes are likely to be achieved through timely recognition of patients at risk of progression and early use of appropriately targeted therapies to prevent irreversible organ damage.