Inappropriate antibiotic use and resistance are major public health challenges. Interventional strategies require ascertaining the perceptions of major stakeholders and documenting the challenges to changing practice. Towards this aim, a qualitative study was conducted in Vellore, South India, using focus group discussions among doctors, pharmacists and public. There were eight groups with six to eight participants each. The themes explored were: understanding of infections, antibiotics and resistance; practices and pressure driving antibiotic use; and strategies for appropriate use. Data were transcribed, analysed, verified and a summary prepared with salient features and quotations. It was found that the public had minimal awareness of resistance, antibiotics and infections. They wanted symptomatic relief. Doctors reported prescribing antibiotics for perceived patient expectations and quick recovery. Business concerns contributed to antibiotics sales among pharmacists. Pharmaceutical industry incentives and healthcare provider competition were the main ethical challenges. Suggested interventional strategies by the participants included creating public awareness, better healthcare provider communication, improved diagnostic support, strict implementation of guidelines, continuing education, and strengthening of regulations. Perceived patient benefit, unrestricted autonomy and business-cum-industry pressures are promoting inappropriate use of antibiotics. Strategies improving responsible use will help preserve their effectiveness, and provide distributive justice and benefit for future generations.