The need for effective antibiotics to manage the ever increasing frequency of antibiotic-resistant gram-positive infections in much of the developed world has led to the clinical development of the first oxazolidinone antibiotic, linezolid. Linezolid possesses bacteriostatic activity against both antibiotic-susceptible and resistant strains of staphylococci, enterococci, and streptococci of relevance to human infection. Clinical trials have confirmed its effectiveness in the treatment of serious infections of skin and soft tissue and the lower respiratory tract. Linezolid has also provided improved outcomes in the treatment of serious vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus infections in a compassionate use program. Emergence of linezolid-resistant gram-positive cocci during clinical use has recently been described, suggesting that its present role in therapy should be reserved for the treatment of antibiotic-resistant gram-positive infections.