In the century and a quarter since William Osler delivered his framed lectures on endocarditis substantial advancements have occurred in the understanding and treatment of this disease. This article summarizes current understanding of endocarditis in the areas of population epidemiology, host factors, microorganisms, diagnosis, and therapy. In addition, the authors discuss possible directions for investigation in the future, including a new multinational consortium, the International Collaboration on Endocarditis (ICE). This collaboration aims to provide a mechanism to advance the understanding of endocarditis in areas difficult to study without an established network. The multinational nature of the collaboration may also permit a more global view of IE and provide opportunities for studies such as randomized trials of therapeutic treatment strategies.