Approximately 10% of the U.S. population 12 years and older reported using illicit substances in 2015. This article reviews the clinical effects and treatment of persons who use cocaine, methamphetamines, 3,4-methylenedioxymethamphetamine (MDMA), synthetic cannabinoids, and synthetic cathinones ("bath salts"). Cocaine blocks the reuptake of the monoamine transporters dopamine, norepinephrine, and serotonin. Immediate clinical effects include increased energy and euphoria, as well as hypertension and arrhythmias. Acute myocardial infarction, seizures, hallucinations, hyperthermia, and movement disorders are among the possible adverse effects. Like cocaine, methamphetamine blocks reuptake of monoamine transporters, but also stimulates dopamine release and has a longer duration of action. Methamphetamine misuse is associated with severe dental problems. MDMA is a stimulant and psychedelic with a chemical structure similar to serotonin. Adverse effects include serotonin syndrome, hyponatremia, long-term memory impairment, and mood disorders. Synthetic cannabinoids can have a more intense and long-lasting effect than natural cannabis. Acute intoxication may cause severe cardiac and respiratory complications and seizures. Synthetic cathinones are marketed as cheap substitutes for other stimulants. Their effects are similar to those of other stimulants, and they are addictive. Psychosocial intervention is the main form of treatment for addiction to these substances. Promising therapies include disulfiram and substitution therapy for cocaine misuse disorders, and mirtazapine for methamphetamine use disorder.