In vivo brain imaging enables the systematic examination of trait and state variables that contribute to the etiology of human diseases. This review highlights the use of in vivo imaging in nonhuman primate models of drug abuse. In efforts to translate findings from laboratory animals to humans, monkey models offer considerable advantages over those that use rodents and other species because of their neurobiological similarity to humans and their longer life span, which makes it possible to study individual subjects over several years. This article provides a brief overview of positron emission tomography (PET), magnetic resonance imaging (MRI)-based techniques, and encephalographic approaches, with a focus on methodological issues that investigators new to the field should consider. We discuss PET imaging studies involving the dopamine (DA) system, with a special emphasis on DA D2 receptors, and describe experimental approaches through which PET imaging data can provide information about the neuropharmacological and neurochemical actions of drugs that modify behavior. We also consider the use of imaging to understand the impact and interactions of genetic predispositions and environmental and physiological modulators on disease states. For MRI-based and encephalographic studies, we describe approaches that can provide new information about brain function. Although much work remains to be done to adapt and apply these techniques for routine use in nonhuman primates, there has been much progress. These techniques will provide the foundation for future studies aimed at developing behavioral and pharmacological treatments for many human diseases.