Publisher Summary This chapter describes the adverse effects of drugs of abuse. Methamphetamine, which can be taken intravenously, orally, by inhaling, or by smoking, is most often abused intravenously. During the synthesis of methamphetamine, lead acetate, a reagent, occasionally contaminates the drug, resulting in increased lead concentrations in methamphetamine users. The acute serious hepatotoxicity is unusual with one-time methylenedioxymethamphetamin (MDMA) use. It mostly occurs after repeated exposure over weeks to months followed by acute use with strenuous activity. Cocaine toxicity rarely occurs when standard nasal procedures and cocaine doses are used. Cocaine-induced thoracic skeletal muscle injury or transient cocaine-induced coronary vasospasm should be considered as alternative sources of chest pain in patients with cocaine-related chest pain and electrocardiographic abnormalities. Chronic cocaine users have impaired endothelium-dependent vasorelaxation in both small-caliber forearm vessels and large-caliber epicardial vessels. This dysfunctional endothelium can link cocaine use to ischemic events. Transesophageal echocardiography has been used to examine the thoracic aorta and coronary arteries before and after intravenous cocaine use.