Rapidly increasing antimicrobial resistance and lack of effective antibiotics are dilemma in the treatment of infectious diseases. Clinicians are now considering the use of old antibiotics such as colistin, fosfomycin because of limitation of therapeutic options. The unique pharmacokinetic and pharmacodynamics properties of these antibiotics have led the new therapeutic approaches, such as the combination of agents and newer dosing regimens. Colistin has become the last drug of the treatment of multidrug resistant gram-negative bacteria and the loading dose and high dose maintenance has been suggested. Tigecycline is licensed for the treatment of complicated skin and intra-abdominal infections and has broad activity against gram-positive and gram-negative pathogens but cautious use in the treatment of bloodstream infection and pneumonia is recommended. Oral and intravenous fosfomycin may be effective treatment options in the case of resistant gram-negative infections but clinical studies are limited.