The number of discovery proteomic studies of drug abuse has begun to increase in recent years, facilitated by the adoption of new techniques such as 2D-DIGE and iTRAQ. For these new tools to provide the greatest insight into the neurobiology of addiction, however, it is important that the addiction field has a clear understanding of the strengths, limitations, and drug abuse-specific research factors of neuroproteomic studies. This review outlines approaches for improving animal models, protein sample quality and stability, proteome fractionation, data analysis, and data sharing to maximize the insights gained from neuroproteomic studies of drug abuse. For both the behavioral researcher interested in what proteomic study results mean, and for biochemists joining the drug abuse research field, a careful consideration of these factors is needed. Similar to genomic, transcriptomic, and epigenetic methods, appropriate use of new proteomic technologies offers the potential to provide a novel and global view of the neurobiological changes underlying drug addiction. Proteomic tools may be an enabling technology to identify key proteins involved in drug abuse behaviors, with the ultimate goal of understanding the etiology of drug abuse and identifying targets for the development of therapeutic agents.