North America features some of the world’s highest consumption levels for controlled psychoactive prescription drugs (PPDs; e.g. prescription opioids, benzodiazepines, stimulants), with non-medical use and related harms (e.g. morbidity, mortality) rising in key populations in recent years. While the determinants, characteristics and impacts of these ‘use’ problems are increasingly well documented, little is known about the ‘supply’ side of non-medical PPD use, much of which is facilitated by ‘diversion’ as a key sourcing route. This paper provides a select review of the phenomenon of PPD diversion in North America, also considering interventions and policy implications. A conceptual and empirical review of select-peer- and non-peer-reviewed research literature from 1991 to 2010 focusing upon PPD diversion in North America was conducted. The phenomenon of PPD diversion is heterogeneous. Especially among general populations, a large proportion of PPDs for non-medical use are obtained from friends or family members. Other PPD diversion routes involve ‘double doctoring’ or ‘prescription shopping’; street drug markets; drug thefts, prescription forgeries or fraud; as well as PPD purchases from the internet. The distinct nature and heterogeneity make PPD diversion a complex and difficult target for interventions. Prescription monitoring programs (PMPs) appear to reduce overall PPD use, yet their impact on reducing diversion or non-medical use is not clear. Law enforcement is unlikely to reach PPD diversion effectively. Effective reduction will probably require reductions in overall PPD consumption volumes, although such will need to be accomplished without compromising standards of good medical (e.g. pain) care.