OBJECTIVES: Colistimethate sodium (Colistin) is an old, “forgotten” antibiotics revived due to multidrug-resistant Gram-negative bacteria in nosocomial infections. In many countries, both – intravenous and inhalational administrations of Colistin have marketing authorisation. In Serbia, Colistin is registered only for intravenous administration. Therefore, inhalational administration of Colistin in treatment for cystic fibrosis is considered as off label use. AIM:The purpose of this study was to assess benefits of Colistin off label use, currently available in Serbia, for treatment for cystic fibrosis.  METHODS:   Data collected from a review of the literature (Pubmed searching key word off label, Colistin, Tobramycine, cost minimisation) and data from Health Insurance Fond of Republic Serbia (2014)  were used to perform a cost-minimisation analysis comparing DDD in inhalation administration of Colistin with Tobramycin (official methodology in Serbia for drug reimbursement Listing) .  RESULTS: Both, Colistin and Tobramycine are effective in cystic fibrosis treatment. The cost of treatment per patient per year in Serbia is 3 616,00 Euro for Colistin and 5 950,00 Euro for Tobramycin. Total savings per year for 200 registered patients in Serbia could be 466 857,00 Euro.  CONCLUSIONS: Given cost-minimisation analysis justified the treatment with Colistin as cost saving therapeutic alternative to Tobramycin for cystic fibrosis patients in Serbia.The lack of guidelines and principles regarding off label medicine use in health care policy and decision making in Serbia was evidently an obstacle for better patients care.