The aim of the study was to map and analyze general practitioners` opinions of, attitudes towards and experiences with generic drugs and generic substitution (GS) in the Czech Republic. General practitioners (GPs) who took part in the annual and regional professional conferences of the Society of General Practice in the period from November 2008 until March 2009 were asked to complete the 28-item questionnaire concerning the issue of generic drugs and GS. Questions were organized in 5 sections aimed at assessing the attitude towards GS, understanding the legislation and opinions on statements related to GS. All data were analyzed using descriptive statistics and correlations were tested by selected parametric and non-parametric tests. Total of 263 completed questionnaires were returned (mean age of 52.2 years (SD=13.7), 177 (67.3%) females and 248 (94.3%) GPs having a practice specialization). 99 (37.6%) respondents have considered generic drugs to be bioequivalent to the respective brand name drugs. 121 (46.0%) respondents believed that generic drugs are of lower quality than brand name drugs. None of respondent showed acquaintance with all the legal rules for GS. Awareness of the legislation and attitude towards GS correlated with the age (p<0.001). In conclusion, distrust among GPs in generic drugs derives from poor knowledge and personal experiences.