Bacterial infections have an enormous impact on public health, which are combated using antibiotics. The World Health Organization has predicted that drug-resistant disease caused by continuous use of antibiotics could cause nearly 10 million deaths each year by 2050 and catastrophic damage to the economy. With no successful discovery of novel set of antibiotics for nearly four decades, antimicrobial resistance has become a serious public health threat. As human race is already facing a dramatic challenge due to resistance in this antibiotic era, there is an urgent need for alternative therapies to combat this issue. That said, phage therapy – which uses bacterial viruses (phages) to combat bacterial infections and has been around for more than 100 years – is considered a promising alternative to antibiotic therapy, especially against multidrugresistant pathogens. Phage therapy has several advantages over antibiotic therapy: high specificity, i.e., targeting a specific pathogen but not the rest of the microbiome; ability to overcome bacterial biofilms; and ability to deliver novel antimicrobials like CRISPR-Cas nucleases. However, despite holding several advantages, conventional phage therapy technology is not widely successful. In this chapter, we highlight how bacteriophages are used to treat infections caused by pathogens, especially ESKAPE pathogens. We also summarize the currently available methods for bacteriophage genome engineering and discuss the advantages of using genetically engineered bacteriophages over conventional methods to combat bacterial infections.