This chapter reviews the therapeutic efficacy, tolerability and mode of action of modafinil and armodafinil for approved and off-label treatment of excessive sleepiness. The American Academy of Sleep Medicine (AASM) recommends modafinil as standard treatment for residual excessive sleepiness in treated obstructive sleep apnea (OSA) patients. Both modafinil and armodafinil appear to be effective treatments for residual sleepiness in patients with OSA despite continuous positive airway pressure (CPAP) treatment. Armodafinil significantly improves speed of memory, episodic secondary memory, and power of attention. Currently, modafinil and armodafinil are widely used for sleepiness associated with narcolepsy. Armodafinil has recently been approved for the treatment of daytime sleepiness in patients with narcolepsy, shift work disorder (SWD), and sleepiness associated with treated OSA. Modafinil has been used for sleepiness or fatigue in Parkinson's disease, multiple sclerosis, depression, and chronic fatigue syndrome, as well as other neurological and psychiatric disorders.