Promoting the use of generic medicine has provided an opportunity for policy makers to make effective use of medicines. The current study aims to explore the prescribers' knowledge, perceptions and willingness to prescribe generic medicines in Hospital Seberang Jaya Penang State, Malaysia. A cross-sectional survey was conducted using a 23-item questionnaire among physicians practicing at Hospital Seberang Jaya, Malaysia. Data were analyzed using Statistical Package for Social Science (SPSSÕ) version 16. The majority of the respondents 121 (68.4%) were from the age group less than 30 years. Overall, only 7 (4.0%) were aware of the correct National Pharmaceutical Control Bureau's bioequivalence range that was 80-125%. About 81 (45.8%) of the respondents were unaware of the safety of the generic medicines. Nearly one-third, 57 (32.2%), of the respondents had doubts about the efficacy of generic medicines. Most of the prescribers, 159 (89.8%), insisted on the need for the availability of guidelines or a protocol on brand substitution. The majority 152 (85.9%) believed that collaboration between pharmacist and physicians will be an option to promote the quality use of medicines. In physicians' personal perspectives, 81 (45.7%) disclosed that it is simpler for them to remember the brand names and 93 (52.5%) stated that advertisements/marketing by the drug companies will influence their prescription pattern. Malaysian medical graduates were found to have poor knowledge about quality; safety and efficacy of generic medicines were common barriers to generic prescription. Marketing and promotional activities by the pharmaceutical companies will be the potential factors that may affect the prescription practices of the physicians.