The abuse of methamphetamine (METH) continues to increase throughout all age groups in different regions of the United States. "Ice," the popularized jargon for (+) methamphetamine hydrochloride, is the predominant drug form that is now consumed. "Ice" is effectively absorbed after either smoking or snorting and it is this rapid influx of drug that produces effects similar to those after intravenous administration. The intensity of METH actions in the central and peripheral nervous system shows tolerance after chronic administration, indicating that neuroadaptations have occurred. Thus, the physiological processes and corresponding biochemical mechanisms that regulate neuronal function have been changed by METH exposure. These biological alterations contribute to the craving and dependence associated with METH abuse and the withdrawal syndrome upon abstinence. However, these changes in behavior may also result from METH-induced neurotoxicity. This article reviews aspects of METH pharmacokinetics and related molecular pharmacodynamics that represent METH pharmacology and then relates those actions to their potential to produce neurotoxicity in humans.