Over the last several decades, a number of previously known or newly described species of gram-positive bacteria have emerged as important human pathogens, particularly in industrialized countries. These microbes have demonstrated an impressive ability to produce an array of striking infectious diseases never before seen or only infrequently encountered in the past. Despite aggressive therapeutic intervention, many of these conditions portend significant morbidity and mortality. Diseases caused by members of the Staphylococcus and Streptococcus genera have figured prominently in this regard, with Staphylococcus aureus, S. epidermidis, Streptococcus pyogenes, and other beta-hemolytic streptococci being regarded as the most important species. This review focuses on the clinical and microbiologic aspects of key emerging infections caused by this group of microorganisms.