OBJECTIVES Orphan drugs are highly priced and top 20 orphan drugs create almost 2,5% of total drug expenditure in Slovakia. We conducted 8 years review of government and literature sources to provide insight into pricing, reimbursement and availability situation surrounding top 20 orphan drugs in Slovakia from the health care payer perspective.  METHODS We provide analysis of official prices, reimbursement status and availability of top 20 orphan drugs in Slovakia from 2005 till 2012. Data were obtained from government sources.  RESULTS We considered orphan drugs list (Cote and Keating, 2012) that exceeded 1 billion $ sales in 2008 (globally) and compared molecules' availability in Slovakia. Same molecules are among best selling 20 orphan drugs in Slovakia, with highest sale of 95 million EUR (Bevacizumab, 2005-2012) compared to lowest sale of 19 million EUR (Tacrolimus, 2005-2012). It took from 1 (Imatinib) to 19 years (Glatiramer acetate) to be launched in Slovakia after orphan designation. Top 20 orphan drugs had average DOT 472 EUR compared to total pharma market DOT average 0,43 EUR. From selected orphan drugs 60% had full (100%) reimbursement status and 40% were fully covered by hospital budgets. Only 4 of them were launched in Slovakia since 2005 (included), 16 of them were launched from 1990 till 2004. Prices ranged from 330 EUR to 5800 EUR (ex-factory, one package, 2012).                 CONCLUSIONS There are highly valuable incentives for industry to invest in to development of orphan drugs in EU. Current context of economic constraints in EU however justifies the need to pay close attention to the rationale of maintaining such incentives in the context of potential return on investments of companies offering high priced drugs. Top 20 orphan drugs in Slovakia have prices high above average and also full reimbursement status. We expect more restrictive drug policy measures in this field.