Gram-positive cocci account for the large majority of cases of infective endocarditis. Pathogenesis investigations of endocarditis have therefore focused on purported virulence factors in staphylococci, viridans group streptococci and enterococci. In addition to novel molecular techniques that have been adapted for use in the examination of gram-positive cocci, animal models of experimental endocarditis have been employed to support or discount the role of specific bacterial components in production of infective endocarditis. This review details recent work that addresses endocarditis pathogenesis and highlights pertinent findings from these investigations.