This chapter explores the complex relationship of stroke with the usage of abusive drugs. Opiates, amphetamines, cocaine, D-lysergic acid diethylamide (LSD), marijuana, sedatives, ethanol, tobacco and phencyclidine are investigated. Hemorrhagic stroke in heroin users may be a consequence of hepatitis with liver failure and deranged clotting or of heroin nephropathy with uremia or malignant hypertension. Amphetamine-induced cerebral vasculitis has also caused ischemic stroke. Cocaine increases the likelihood of vasospasm after aneurysm rupture. D-lysergic acid diethylamide (LSD), phencyclidine and marijuana users reports symptoms of stroke. Barbiturates, benzodiazepines, and other sedative drugs can cause cerebral infarction whereas hemorrhagic stroke has not otherwise been reported. Aneurysmal rupture occurred during orgasm following amyl nitrite inhalation. Multiple mechanisms probably explain the complex association of ethanol and stroke. Smoking is a major risk factor for coronary artery and peripheral vascular disease. Tobacco increases the risk for both ischemic and hemorrhagic stroke.