The prevalence of vancomycin resistance is steadily rising among clinical isolates of Enterococcus spp., thereby limiting the treatment options for infections caused by vancomycin-resistant enterococci. The precise nature of the glycopeptide resistance genes has been elucidated, and many studies on gene reservoirs and strain-versus-resistance-gene epidemiology have been performed. The prevalence of vancomycin-resistant enterococci in various clinical and environmental settings in relation to nosocomial and veterinary applications of antimicrobial glycopeptides is discussed in detail in this review. Novel molecular tools for the identification of vancomycin-resistant enterococci genomes or the various resistance genes have been applied in order to expand current insight into the overall epidemiology of the resistance trait itself. The risk of the spread of vancomycin resistance to other bacterial species was recently underscored by the emergence of staphylococci showing clinical resistance to vancomycin. The topics mentioned above are elaborated on and discussed in light of the increasing medical concern on the future detection of microbial infections beyond chemotherapeutic cure.