Many advances in the conceptualization of addiction as a disease of the brain have come from the application of imaging technologies directly in the human drug abuser. New knowledge has been driven by advances in radiotracer design and chemistry and positron emission tomography (PET) and single-photon emission computed tomography (SPECT) instrumentation and the integration of these scientific tools with the tools of biochemistry, pharmacology, and medicine. This topic cuts across the medical specialties of neurology, psychiatry, oncology, and cardiology because of the high medical, social, and economic toll that drugs of abuse, including the legal drugs, cigarettes and alcohol, take on society. This article highlights recent advances in the use of PET and SPECT imaging to measure the pharmacokinetic and pharmacodynamic effects of drugs of abuse on the human brain.