Bupropion holds a unique place due to its different pharmacological mechanism—dopamine and norepinephrine reuptake inhibition—with an overall mild but consistent activating effect. Bupropion is often used off-label by sleep specialists to reduce excessive daytime sleepiness and can result in difficulty with sleep onset if it is taken later in the day. This unique mechanism of action is shared with a newer agent, solriamfetol, which has been approved for the indication of excessive daytime sleepiness in narcolepsy and residual sleepiness associated with OSA despite treatment.