Prudent, rational, and targeted use of antimicrobials in plant production maximizes their therapeutic efficacy while reducing the risk of development of resistance and environmental contamination improving food safety. Here we present the four principles of effective and responsible use of antimicrobials in plant production namely, i) reduce the need for antimicrobials, ii) manage plant disease with minimal antimicrobials iii) follow antimicrobial use directions carefully, and iv) dispose unused/expired antimicrobials and containers safely.