There is currently no consensus on how best to manage refractory immune thrombocytopenic purpura (ITP). In part, this reflects the need for individualized treatment due to the wide spectrum of patients' requirements and responsiveness to therapies. The objective of this review is to provide a clinically useful guide to current management strategies. This article suggests investigations to identify factors that may exacerbate thrombocytopenia and underlie poor therapeutic responses, and highlights emerging therapies, including the thrombopoietic agents, which are anticipated to dramatically alter the natural history of “refractory” ITP. Morbidity, mortality and heath-related quality of life are also discussed.