The development of antibiotic resistance in bacteria is a growing concern. This situation demands a search for antibiotic alternatives. Bacteriophages—natural viral predators of bacteria—are viewed as a possible alternative to treat bacterial infections. Many clinical trials today have not found phages effective as therapeutics. Some of the major challenges regarding usage of bacteriophage as a therapeutic have been: horizontal evolution of bacteria, limited host range of bacteriophage, removal of endotoxins in preparations, the technical feasibility of isolation, mode of administration, rapid clearance and immune rejection.These issues have been addressed in this review. Applications of genetic engineered phages and other remarkable non-human applications are also discussed.