The discovery of the growth promoting property of antibiotics led to their use as antibiotic feed additives (AFAs) in animal feed at sub-therapeutic doses. Although this has been beneficial for animal health and productivity, it has been, essentially, a double-edged sword. The continued and non-judicious use of AFAs has led to the selection and dissemination of antibiotic-resistant strains of poultry pathogens such as Salmonella, Campylobacter and Escherichia coli. The rapid spread of drug-resistant pathogens as well as emergence of antibiotic-related environmental pollutants is of global concern. Hence, the identification and development of new and effective alternatives to antibiotics that do not hinder productivity is imperative. For this, it is essential to understand not only the molecular basis of development of resistance to AFAs but also the mechanisms of action of AFA alternatives and how they differ from AFAs. This review provides a molecular perspective on the alternatives to antibiotics that have been proposed till date and their current trends, as well as novel approaches such as development of improved delivery systems.