Over the last decade the proliferation of antibiotic-resistant pathogens has been a growing problem, especially in some geographic areas, making useless most of the classical antibiotic therapies. The rapid emergence of resistant bacteria is the result of different factors as the intrinsic microbial complexity, the growing attitude to travel of humans, animals and goods, the use of antibiotics outside hospitals, and the lack of precise therapeutic chooses for high risk group of patients. The antibiotic-resistance becomes certainly a serious problem when a resistant pathogen, and often multi-resistant today, is present in an infective site. In fact in a recent estimate of the Centre for Disease Control and Prevention (CDC) about 90.000 deaths per year in the USA are attributable to bacterial infections and in particular to resistant pathogens. It appears clear that the clinic relevance of this problem is the decimation of the sensible germs of the normal flora that leads to the upper hand of the only resistant bacteria. The antibiotic therapy, in fact, select the resistance and each bacteria has developed a particular strategy to survive: mutations of the genetic content or acquisition of resistance genes from the external. Among the Gram positive bacteria, besides methicillin resistant Staphyloccocus aureus, there are other pathogens such as coagulase-negative staphylococci (CoNS), Enterococcus faecium and Enterococcus faecalis, some species of streptococci and multiresistant Corynebacterium. The CoNS, eg. S. epidermidis, S. hominis and S. haemolyticus, are recognized as new important nosocomial pathogens and are not only responsible of invasive infections but have become in few years resistant to oxacillin (more than 60%) and multiresistant. The unsuspected fragility of glycopeptides, which for 40 years have been the most important treatment against infections due to Gram-positive bacteria, has posed the need for new antimicrobial molecules. Among the therapeutic possible options there are linezolid, tygecyline and daptomycin, but new other molecules are appearing in the clinical use like ceftobiprole and dalbavancin.