Publications reported on studies of eculizumab for 39 distinct indications including 8 non-malignant and 1 malignant hematologic disorders, 6 autoimmune disorders, 6 transplant-related indications, and 5 renal disorders. Among FDA-approved indications, for only 2, paroxysmal nocturnal haemoglobinuria and myasthenia gravis, were there confirmatory trials published. The authors warn that increasing net sales of eculizumab in the context of FDA approval for only 3 rare indications raises concern that off-label use may now represent a substantial proportion of revenue for eculizumab, and patients and clinicians should be aware that the evidence supporting off-label use consists mostly of case series/case reports, along with small observational and interventional studies.