The basic problems of staphylococcal infections do not seem near to solution. Possibly an effective and safe antibiotic will be found to which resistant, pathogenic staphylococcal mutants will not appeal. This may, not be an overly sanguine hope. Had it not been for the ability of the staphylococcus to synthesize penicillinase, this goal would have been achieved already, for staphylococcal mutants pathogenic to man and intrinsically resistant to penicillin (i.e., without the production of penicillinase) have not been reported. Even with better antibiotics grave problems would remain, however, for the staphylococcus often inflicts severe or even irremediable damage, especially in the heart, before the disease can be diagnosed. Prevention is the crucial problem. Refinements in isolation technics and hospital sanitation may improve the protection of the patient in the operating room and the newborn infant in the nursery. Nevertheless, the hard core of infections in debilitated or otherwise susceptible medical patients will probably remain. To help them it will be necessary to learn to restore the mechanisms of normal host resistance that have been depleted by disease.