Kyowa Hakko Kirin is developing istradefylline, a selective adenosine A2A receptor antagonist, for the once-daily oral treatment of Parkinson's disease (PD). Adenosine A2A receptors are considered to be present particularly in the basal ganglia of the brain; the degeneration or abnormality observed in PD is believed to occur in the basal ganglia, which is recognized to play a significant role in motor control. Commercially available dopamine replacement therapies effectively treat the early motor symptoms of PD; however, these agents are associated with development of motor complications, limiting usefulness in late stages of the disease. Istradefylline is proposed to possess a clearly distinct action site from existing agents which act on dopamine metabolism or dopamine receptors. Kyowa Hakko Kirin has received approval for istradefylline in the adjunctive treatment of PD in Japan. A New Drug Application was filed in the USA, but the FDA issued a non-approvable letter in February 2008. This article summarizes the milestones in the development of istradefylline leading to its first approval for the treatment of patients with PD.