Kah-Lok Chan,1 Stephen Lade,2 H Miles Prince,1,3 Simon J Harrison1,3 1Department of Haematology, 2Department of Anatomical Pathology, Peter MacCallum Cancer Centre, 3Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia Abstract: First described 60 years ago, Castleman disease comprises a rare and heterogeneous cluster of disorders, characterized by lymphadenopathy with unique histological features and associated with cytokine-driven constitutional symptoms and biochemical disturbances. Although unicentric Castleman disease is curable with complete surgical excision, its multicentric counterpart is a considerable therapeutic challenge. The recent development of biological agents, particularly monoclonal antibodies to interleukin-6 and its receptor, allow for more targeted disease-specific intervention that promises improved response rates and more durable disease control; however, further work is required to fill knowledge gaps in terms of underlying pathophysiology and to facilitate alternative treatment options for refractory cases. Keywords: Castleman disease, angiofollicular lymph node hyperplasia, biologics, siltuximab, tocilizumab, rituximab