Objectives: Modafinil is a waking drug prescribed to narcolepsy patients, but its usage among healthy individuals is increasing to enhance their alertness or to mitigate fatigue. This study was conducted to investigate practical use and toxic effects on neuro-immune interaction of modafinil. Methods: This study reviewed the significance of psychoactive drugs, and discussed the benefits and risks of the application of modafinil, which seems to be ideal as an anti-psychotic or anti-fatigue agent. Results: Modafinil is known to have less or no adverse effects than those found in traditional psychostimulants such as amphetamine, methylphenidate or cocaine. It can be applied as an anti-psychotic or anti-fatigue agent. However, the waking mechanism of modafinil is yet to be fully revealed. Recent studies reported that modafinil may be subject to abuse and addiction. In addition prolonged sleeplessness induces stress responses and impairs immune function. Conclusions: Modafinil can be used by anyone, who wishes to work late, stay awake, enhance their cognitive reactions, or brighten their moods. Users may already be under a great level of stress, i.e. cancer patients or soldiers in a battle field. A psychoneuroimmunological approach is thus needed to investigate the multi-functional effects of modafinil.