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Decades later, it is not uncommon for gram\u2010negative organisms to be multidrug\u2010resistant and even pan\u2010resistant to available antibiotic regimens, leaving clinicians with few therapeutic alternatives. Because fosfomycin has been shown to retain activity against these virulent pathogens, there is renewed interest in its use as a therapeutic agent. Fosfomycin formulations including fosfomycin disodium and the newer tromethamine salt are less toxic than other alternatives and are attractive options for resistant gram\u2010negative and gram\u2010positive infections. Oral fosfomycin tromethamine is approved for urinary tract infections in the United States, and an intravenous formulation is also available outside of the United States for systemic disease. The bactericidal action of fosfomycin occurs at an earlier step in cell wall synthesis than that of \u03b2\u2010lactam antibiotics. From an in vitro standpoint, fosfomycin generally has high activity against <jats:styled-content style=\"fixed-case\">ESBL<\/jats:styled-content>\u2010 and carbapenemase\u2010producing Enterobacteriaceae; multidrug\u2010resistant <jats:italic>Pseudomonas aeruginosa<\/jats:italic> susceptibility appears to be more dependent on the local antibiogram. Fosfomycin formulations have a large volume of distribution, penetrate biofilms, and concentrate in the urine. Both oral and intravenous fosfomycin formulations are effective for a wide range of gram\u2010negative infections and disease severities; however, clinical studies are limited. Fosfomycin formulations are well\u2010tolerated, and mild gastrointestinal distress is the most common adverse effect. The primary limitations of fosfomycin are the lack of established regimens for complicated infections and the lack of availability of the intravenous formulation in the United States. 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