The shortage of new antimicrobial agents has made the scientific community reconsider the potential value of old antibiotics. A search of the literature was performed to compile relevant evidence regarding the effectiveness and safety of fosfomycin for the treatment of patients with gram-positive and/or gram-negative bacterial infections (excluding urinary tract infection and gastrointestinal infection). Of 1311 potentially relevant studies, 62 studies were reviewed in detail. Of 1604 patients with various gram-positive and gram-negative infections of various body sites (including pneumonia and other respiratory infections; osteomyelitis; meningitis; ear, nose, and throat infections; surgical infections; obstetric and gynecological infections; arthritis; septicemia; peritonitis; cervical lymphadenitis; eye infections; diabetic foot infections; and typhoid fever) being treated with fosfomycin alone or in combination with other antibiotics, cure was achieved in 1302 (81.1%) of the patients, and improvement was noted in 47 (2.9%). In comparative perioperative prophylaxis trials that included a total of 1212 patients (mainly patients undergoing colorectal surgery), the fosfomycin-metronidazole combination led to results that were similar to those achieved with the combination of other antibiotics (doxycycline, ampicillin, or cephalothin) and metronidazole. In an era in which there is a shortage of new antibiotics, fosfomycin might be considered to be an alternative treatment agent for infections caused by gram-positive and gram-negative bacteria, in addition to its traditional use in treating uncomplicated urinary tract and gastrointestinal infections. Further research on the in vitro antimicrobial activity of fosfomycin, especially against multidrug-resistant pathogens (such as extended-spectrum beta-lactamase-producing and/or metallo-beta-lactamase-producing enterobacteriaceae and Pseudomonas aeruginosa, and on the effectiveness and safety of the drug in the treatment of patients with such infections may be warranted.