The intake of a large variety of substances has a negative impact on sleep. Widely used, readily available substances like alcohol, nicotine, or caffeine need to be mentioned here. Illicit drugs (e.g., heroin or ecstasy) have different mechanisms of action with a high sleep-disrupting potential. Prescription drugs, i.e., corticosteroids or β-blockers, may also negatively affect sleep. An important question is whether the intake of hypnotics, especially benzodiazepines, may have a negative long-term effect on sleep. Classical benzodiazepines (BZ) initially lead to a reduction of nocturnal wake time and prolong total sleep time as a desired effect. Regarding the microstructure of sleep, BZ lead to a reduction of slow frequencies and an increase of fast frequencies in the EEG. With many BZ, tolerance may occur, thus, leading to unwanted dose increases. Further problems include rebound effects that occur upon discontinuation of BZ, including a drastic deterioration of sleep upon drug withdrawal. This phenomenon may pave the way for the development of drug dependency. Further unwanted side-effects (e.g., nocturnal falls) and the question of BZ abuse and dependency will be discussed.