OBJECTIVES The lack of information and scientific knowledge of rare diseases (RDs) and orphan drug (ODs) could affect the quality of health care delivered to patients suffering from rare diseases. The aim of this study was evaluation of the level of the general epidemiological knowledge among pharmacists regarding RDs and ODs as well as how that  knowledge is influenced by information sources, education level and years of experience. METHODS The research design was based on a descriptive cross-sectional study. A questionnaire previously used in a pilot KAP study in Serbiain2012 was applied. The respondents were 182 pharmacists from public pharmacies in seven of 29 districts in Serbia. Individual level of knowledge was assessed by total number of correct answers from a maximum of 9, and overall knowledge was an average of the individual level of knowledge. RESULTS In total, 155 pharmacists were included in the full analysis set (response rate was 86.3%). Overall, the mean age was 43.4 years, and 94% were women. The average number of information sources regarding RD was 1.7%, and mostly one source out of five was used (56.1%). Pharmacists who were engaged in post-graduate programmes or completed such programmes tended to use more sources of information (69.2%) than those who were not involved in any such programme (41.9%). The mean value of correct answers about pharmacists’ knowledge regarding RD and OD was 4 ± 1.77. Most pharmacists (n = 30, 19.35%) replied correctly to 6 questions.  CONCLUSIONS The results indicate that years of experience and age among pharmacists do not have influence to the overall knowledge about RD. The positive impact of education was evidently, and for the better pharmaceutical care of RD patients the training of pharmacists to proper use of professional sources of information should be usefully.