The orexin system plays a key role in the control of eating, sleeping and rewarding. This review summarizes the latest developments in the identification of orexin receptor antagonists. By using a selective orexin-1 receptor antagonist, SB-334867-A (GlaxoSnzithKline plc), the in vivo futctions of both the orexin-1 and orexin-2 receptors have been elucidated. This review also sunmmarizes the literature and current opinions up to May 2006 on the therapeutic utility of orexin receptor antagonists for the treatment of eating disorders, sleeping disorders and drug addiction.