Infections caused by gram-positive bacteria have become the most important cause of infectious morbidity among some groups of immunocompromised patients over the last decade. Among the gram-positive bacteria, the emerging problems of resistance to antimicrobial agents include the development of resistance to beta-lactam and aminoglycoside drugs among the enterococci, making synergistic bactericidal therapy impossible; the continued spread of methicillin-resistant staphylococci; resistance to both vancomycin and teicoplanin among enterococci and staphylococci; the emergence of intrinsically vancomycin-resistant species as important pathogens; and resistance to the fluoroquinolones. It is unlikely that new therapeutic classes of antibacterial drugs will be released this decade. Therapeutic alternatives now include unusual combinations of antibiotics to which the strains may appear resistant but that exhibit synergistic activity, although this area has not yet been thoroughly explored. Therefore, control of emergence and spread of resistance through the more judicious use of existing agents, good infection control practices, and the use of imaginative combination therapy for those infected with resistant strains seem to be our best alternatives.