Pharmaceutical expenditure as has been increasingly grown during the last decades so that policy makers have paid more and more attention to develop strategies to deal with this challenging issue.   Pharmacists play an important role in health continuum to implement such strategies through dispensing and delivering generic medicines to consumers.  So, the main objective of this study was to explore the perception of Iranian pharmacists regarding generic substitution, and also to explore how Iranian pharmacists think about patients’ role, physicians’ role and government role in generic substitution. A cross sectional descriptive study involving the entire population of Tehran community pharmacies (n = 2000) was performed using a self-administrated anonymous questionnaire. A total of 1205 questionnaires were returned indicating a response rate of 60%. Regarding to the first section, 62 % of participants agreed that pharmacists should be given right to generic substitution, and 45% viewed that the generic medicine are bioequivalent with brand ones. Majority of the respondents (73.6%) stated that, they do substitution once generic medicine is available. However, they think that patients, physicians and government have   important role in generic substitution. More than half (75.5%) of pharmacists believed physicians’ prescription behavior highly influenced by the marketing and promotion activities of foreign companies. 93% of respondents pointed to full coverage of generic medicines by providers as a strategy to generic substitution.    Summary, evidences indicated that Iranian pharmacists have good insights regarding implementation and promotion of generic substitution strategy.