Many species of Gram-positive cocci are pathogenic. The most important are staphylococci, streptococci, and enterococci. Widespread usage of antibiotics was the main cause for the appearance and spread of resistance to almost all antimicrobials. The occurrence, mechanisms, and genetic background of resistance to antimicrobial drugs other than betalactams and glycopeptides among pathogenic staphylococci, streptococci, and enterococci are discussed in the text. Well-established agents (such as macrolides, lincosamides, streptogramins, aminoglycosides, quinolones, mupirocin, chloramphenicol) as well as new agents (linezolid, daptomycin, quinupristine/dalfopristine, ratapamulin, tigecycline, iclaprim and new generations of quinolones) are considered.