Hospital infection due to multidrug-resistant Gram-positive bacteria may often represent a life-threatening challenge; thus, to appropriately combat them, clinicians should be confident and systematically apply several important pharmacodynamic concepts. The concept of 'correct antibiotic treatment' should include, in addition to an appropriate choice in terms of antimicrobial susceptibility, an appropriate dosage and administration schedule consistent with the pharmacodynamic principles. In the next few years, it is expected that some of the anti-Gram-positive antimicrobial agents that are currently under investigation will be added to the therapeutic armamentarium. However, optimization of the usage of old drugs still remains a clinical priority and a scientific challenge, whose dignity may be considered of similar importance to that of the assessment of the possible therapeutic role of the new compounds.