OBJECTIVES: There are currently 68 orphan drugs with European marketing authorization with orphan designation and 75 orphan drugs without prior orphan designation in EU. Current Health technology appraisal recommendations in Slovak Republic do not include any specific guidelines for reimbursement of orphan drugs (OD). Orphan drug reimbursement decisions are made on case-to-case basis and no clear rules are currently present. We evaluated market uptake of selected 90 orphan drugs and compared it to total market evolution from 2005 to 2012. METHODS: Our analysis include volume and sales evolution of 90 orphan drugs in Slovak Republic from 2005 to 2012 using Health database and publicly available data.  RESULTS: Results show that cumulative 8-years expenditure for selected list of ODs is over 1,1 billion EUR. The peak sale was reached in 2012 and that sale accounted for 18,6% from total pharmaceutical spending in 2012. The highest sales growth was in 2006 with 33,4% compared to previous year. Until 2009, we have seen strong double-digit growth following by still high single digit growth in 2010 (6,1%) and 2012 (7,6%). Total expenditure represented 10,7%, 12,4%, 12,8%, 13,5%, 14,7%, 15,2%, 16,5% and 18,6% of total medicine expenditure from 2005 to 2012 in SK, respectively. The highest expenditure burden lies on one ATC category: L- antineoplastic and immunomodulating agents with 57% share.  CONCLUSIONS: The uptake of orphan drugs is according to EU standards very high, but it must be noted that many ODs are locally off-patent and generics expand the market. Secondly, we included into our selection ODs with and without prior orphan designation. Nevertheless, it is important to make more detailed analysis and advocate for prudent reimbursement rules for orphan drugs, mainly from local HTA perspective.