Psychostimulants have been used routinely for the treatment of the disabling daytime sleepiness associated with narcolepsy. However, the perceived and real potential for abuse of amphetamine and amphetaminelike stimulants prompted a search for new wake-promoting compounds with lower dependency and abuse liabilities. Modafinil is a novel wake-promoting agent with a mechanism of action that differs markedly from that of amphetamine and amphetamine-like stimulants. In controlled clinical trials, modafinil has been shown to be an effective and well-tolerated treatment for excessive daytime sleepiness (EDS) in patients with narcolepsy. With a benzhydrylsulfinylacetamide structure, modafinil has a low level of solubility in water (< 1 mg/mL) and is unstable at temperatures > or = 180 degrees C, physicochemical properties that reduce the potential for its abuse via intravenous injection and smoking, respectively. Available preclinical and clinical data on the abuse liability of modafinil suggest a much lower potential for abuse and dependency than amphetaminelike stimulants commonly used for treating EDS in patients with narcolepsy. Therefore, modafinil represents a valuable therapeutic option for the treatment of EDS associated with narcolepsy.