This is a brief summary of four problems of antibiotic resistance in gram positive bacteria. Methicillin-resistant Staphylococcus spp. remain a major nosocomial threat and have become even more important with the increased use of foreign material (e.g. vascular catheters). There has been a rapid increase in penicillin-resistant Streptococcus pneumoniae isolates. This will lead to a reevaluation of the therapy of common respiratory tract infections such as otitis, sinusitis, and pneumonia, and will create major problems for the empirical treatment of bacterial meningitis. In Group A R-haemolytic Streptococcus spp., resistance to penicillin is unlikely to emerge, but increasing use of erythromycin and other macrolides has resulted in widespread macrolide resistance. Finally, the appearance of multi-resistant Enterococcus spp. shows that we have returned to the pre-antibiotic era. These strains are resistant to all available antibiotics and have caused hospital outbreaks of untreatable and fatal infections.