Bacteriophage therapy for drug-resistant Staphylococcus aureus infections is a promising alternative to traditional antibiotics, especially as antibiotic resistance continues to rise. This review summarizes the current understanding of phage biology, their mechanisms of action, and their application in treating drug-resistant S. aureus infections. Phages are viruses that infect bacteria and can lyse them, making them effective against bacterial infections. They have been used historically for treating infections before antibiotics were widely available but were later replaced due to limited understanding and inefficient production methods. Recently, phage therapy has regained attention due to the growing problem of antibiotic resistance. Phages are classified into two main types: lytic phages, which replicate and kill bacteria, and temperate phages, which can integrate into the bacterial genome. Phage therapy offers several advantages over traditional antibiotics, including high specificity, reduced risk of resistance development, and the ability to target biofilms. In vitro studies have shown that phages can reduce bacterial colonies and enhance the effectiveness of antibiotics. Animal studies have demonstrated that phage therapy can effectively reduce drug-resistant S. aureus infections, with some phage cocktails showing significant efficacy against MRSA and other resistant strains. Clinical trials have also shown promising results, with phage therapy being safe and effective in treating drug-resistant S. aureus infections. Phage therapy has been used in combination with antibiotics, and some studies suggest that it can enhance the effectiveness of antibiotics while reducing the risk of resistance. However, challenges remain, including the need for further research to establish standardized protocols and regulatory frameworks for phage therapy. Endolysins, which are enzymes produced by phages, have also shown promise in treating drug-resistant S. aureus infections. These enzymes can break down the bacterial cell wall, leading to bacterial death. However, lysins can be degraded by gastric acid and proteases, which can be mitigated through encapsulation technologies. Overall, phage therapy and endolysin therapy represent important alternatives to traditional antibiotics in the fight against drug-resistant bacterial infections.Bacteriophage therapy for drug-resistant Staphylococcus aureus infections is a promising alternative to traditional antibiotics, especially as antibiotic resistance continues to rise. This review summarizes the current understanding of phage biology, their mechanisms of action, and their application in treating drug-resistant S. aureus infections. Phages are viruses that infect bacteria and can lyse them, making them effective against bacterial infections. They have been used historically for treating infections before antibiotics were widely available but were later replaced due to limited understanding and inefficient production methods. Recently, phage therapy has regained attention due to the growing problem of antibiotic resistance. Phages are classified into two main types: lytic phages, which replicate and kill bacteria, and temperate phages, which can integrate into the bacterial genome. Phage therapy offers several advantages over traditional antibiotics, including high specificity, reduced risk of resistance development, and the ability to target biofilms. In vitro studies have shown that phages can reduce bacterial colonies and enhance the effectiveness of antibiotics. Animal studies have demonstrated that phage therapy can effectively reduce drug-resistant S. aureus infections, with some phage cocktails showing significant efficacy against MRSA and other resistant strains. Clinical trials have also shown promising results, with phage therapy being safe and effective in treating drug-resistant S. aureus infections. Phage therapy has been used in combination with antibiotics, and some studies suggest that it can enhance the effectiveness of antibiotics while reducing the risk of resistance. However, challenges remain, including the need for further research to establish standardized protocols and regulatory frameworks for phage therapy. Endolysins, which are enzymes produced by phages, have also shown promise in treating drug-resistant S. aureus infections. These enzymes can break down the bacterial cell wall, leading to bacterial death. However, lysins can be degraded by gastric acid and proteases, which can be mitigated through encapsulation technologies. Overall, phage therapy and endolysin therapy represent important alternatives to traditional antibiotics in the fight against drug-resistant bacterial infections.