 Bacterial infections caused by antibiotic resistant isolates have become a major health concern due to their difficulty to treat, resulting in an increase in morbidity and mortality. Phosphomycin is a broad-spectrum bactericidal antibiotic that inhibits cell-wall biosynthesis in both gram-negative and gram-positive bacteria. It has a unique mechanism of action and blocks the enzyme, Mura, which is involved in peptidoglycan synthesis. Phosphomycin has been used successfully for the treatment of urinary tract infections for a long time, but its increasing use as a therapeutic agent has led to the emergence of antibiotic resistance. This resistance can be acquired through several different mechanisms, such as modifying the antibiotic target, reducing antibiotic uptake or inactivating the drug. These mechanisms are discussed in detail, along with their implications in clinical isolates. This article was authored by Alexandro Rodriguez Rojas, Jesus Blazquez, and Alfredo Castaneda Garcia. We are article.tv, links in the description below.