Incidence of Gram-positive infections caused by bacteria resistant to commonly used antibiotics has increased in the last decades. Resistant strains appeared later in the Czech Republic, however their number has been increasing and new antibiotics have to be used. The greatest increase of frequency can be seen in infections caused by methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci. Vancomycin-resistant enterococci are usually found in hematooncology patients. Curative use of vancomycin is limited due to a narrow spectrum of activity, nephrotoxicity, and limited penetration into tissues (lung) and cerebrospinal fluid. Linezolid is a good option mainly in infections of skin and soft tissues, and it has an evincible advantage over vancomycin in the treatment of nosocomial pneumonia and surgical-site infections. Oral formulations are favourable allowing switch therapy and earlier discharge from hospital.