OBJECTIVES: Payers in the U.S. are increasingly employing aggressive cost sharing strategies for specialty drugs. We conducted a systematic review of the published evidence on the associations between patient cost sharing and use of specialty drugs, use of non-drug medical services, and health outcomes and spending.  METHODS: A MEDLINE search for U.S.-based studies published in English between 1995 and 2013 was conducted using various combinations of terms for cost sharing and specialty drugs and/or common conditions for which they are indicated. Additional studies were obtained from reference lists of identified studies.  Key methodological elements of the included studies were extracted and findings were captured to determine effects of cost sharing. RESULTS: We identified 15 articles that focused on one or more diseases, including MUltiple Sclerosis (n=8), cancer (n=7), Rheumatoid Arthritis (n=5), and other conditions (n=4). Majority of the studies (n=14) used administrative claims data on privately insured patients from the year 2009 or earlier, during which time few private insurers were employing aggressive cost sharing for specialty drugs. Outcomes included prescription abandonment (n=2), initiation or any utilization (n=7), adherence (n=8), persistence/discontinuation (n=6), number of claims (n=1), and drug spending (n=1). Findings generally indicated reductions in specialty drug utilization associated with higher cost sharing. However, the evidence was not consistent; the magnitude and/or statistical significance of the effects of cost sharing varied by disease and type of outcome. None of the studies examined the effect of specialty tier cost sharing seen under Medicare Part D or health insurance exchanges; or the effect of cost sharing on medical utilization, spending, or health outcomes.  CONCLUSIONS: Evidence till date generally indicates reductions in specialty drug utilization associated with higher cost sharing, with effects varying by type of disease and specialty drug outcome. We draw upon our findings and the gaps in evidence to summarize future directions for research and policy.