Gram-positive infections have increased in recent years, particularly those that are of nosocomial origin, leading to a broad use of agents with activity against these pathogens. Concomitantly, antimicrobial resistance of these pathogens also became widespread. Among the most common Gram-positive resistant pathogens are: Streptococcus pneumoniae, resistant to penicillin and macrolides, methicillin-resistant Staphylococcus aureus (MRSA), glycopeptide- intermediately-resistant S. aureus (GISA), methicillin-resistant S. epidermidis, glycopeptide-resistant enterococci and vancomycin-resistant enterococci (VRE). The response of the pharmaceutical industry to this challenge was the development of new antibiotics active against these pathogens. Among these antibiotics, this review will focus on: linezolid, an oxazolidinone; GAR-936, a tetracycline derivative; daptomycin, a lipopeptide; and ortivancin (LY-333328), a glycopeptide related to vancomycin. Except for linezolid, which has been recently launched in many countries, all other agents referred to in this review are still at various developmental stages. It is hoped that in the near future most of these agents will be approved and thus the grim outlook of patients infected with resistant Gram-positive bacteria may improve.