OBJECTIVES: CDC has classified prescription drug abuse an epidemic with significant societal economic burden.  A 2009 systematic review on economic burden of prescription opioid misuse and abuse (POMA) found total cost (US, 2001) was ~$8.6 billion and abusers’ annual medical costs were ~$14,000 higher than nonabusers. The objective of this research was to update and synthesize all evidence around prevalence and costs of opioid abuse. METHODS: A systematic review was conducted to update the 2009 results by reviewing worldwide literature involving humans published in English from 2009-2014. The primary focus was prevalence and cost of POMA.  Sources included PubMed, Embase, OpenSIGLE (for gray literature) and others.   RESULTS: CONCLUSIONS: Although comparison of societal costs is difficult given differences in methodology and years studied, societal costs increased from $8.6 billion in 2001 to over $55.7 billion in 2007. POMA is a societal problem and requires action by government, opioid manufacturers, practitioners and payers.