Intrinsic resistance to vancomycin in Gram-positive bacteria presumably predates acquired vancomycin resistance in enterococci but it has only recently generated interest. Intrinsically-resistant enterococci possessing thevanC gene and the non-enterococcal genera Leuconostoc, Lactobacillus, Pediococcus and Erysipelothrix are known to cause human infection. This review examines the available data on their identification, resistance mechanisms, epidemiology, clinical infections and antimicrobial susceptibility. Intrinsically vancomycin-resistant Gram-positives are usually opportunistic pathogens. Although serious infections may occur, treatment options remain available. No additional infection control measures for the intrinsically-resistant genera appear justified with currently available evidence, although vigilance should be maintained to detect future changes in susceptibility patterns.