Multidrug-resistant organisms are an established and growing worldwide public health problem and few therapeutic options remain available. The traditional antimicrobials (glycopeptides) for multidrug-resistant Gram-positive infections are declining in efficacy. New drugs that are presently available are linezolid, daptomicin and tigecycline, which have well-defined indications for severe infections, and talavancin, which is under Phase III trial for hospital-acquired pneumonia. Unfortunately the therapies available for multidrug-resistant Gram-negatives, including carbapenem-resistant Pseudomonas aeruginosa, Acinetobacter baumannii and Enterobacteriaceae, are limited to only colistin and tigecycline. Both of these drugs are still not registered for severe infections, such as hospital acquired pneumonia. Consequently, as confirmed by scientific evidence, a multidisciplinary approach is needed. Surveillance, infection control procedures, isolation and antimicrobial stewardship should be implemented to reduce multidrug-resistant organism diffusion.