Beta-lactams are the most frequently used antimicrobials in combating infections. In the case of gram-positive bacteria resistant to beta-lactams, glycopeptides are the first choice. The occurrence, mechanisms and genetic background of the resistance of pathogenic staphylococci, streptococci and enterococci to beta-lactam and glycopeptide antibiotics were discussed. The resistances to well-established antimicrobials, as well as new agents (ceftobiprole, oritavancin, telavancin, dalbavancin) were taken into consideration in the text.