Desmoteplase is a novel, highly fibrin-specific thrombolytic agent in phase III of clinical development. In comparison to alteplase, it has high fibrin selectivity, is associated with minimal or no neurotoxicity, and has no apparent negative effect on the blood-brain barrier. The safety and efficacy of desmoteplase is being studied in the Desmoteplase in Acute Ischemic Stroke clinical trial program. Three studies (Dose Escalation Study of Desmoteplase in Acute Ischemic Stroke, Desmoteplase in Acute Ischemic Stroke, and Desmoteplase in Acute Ischemic Stroke-2) have been completed, two large randomized, double-blind, placebo-controlled, phase III trials are ongoing at >200 sites worldwide (Desmoteplase in Acute Ischemic Stroke-3 and Desmoteplase in Acute Ischemic Stroke-4, n = 800; DIAS-3 and DIAS-4), and a randomized, double-blind, placebo-controlled, dose-escalation phase II trial is ongoing in Japan (Desmoteplase in Acute Ischemic Stroke-Japan, n = 48; DIAS-J).