The risk of intravascular cardiac device infection (ICDI) has increased significantly over the last decade and is rising faster than the corresponding increase in device implantations. ICDIs may consist of pocket infections, wire infections, wire infections complicated by endocarditis, or combinations of these. In this review, we examine the microbiology of ICDIs, focusing on the risk of developing ICDI following bloodstream infections with key pathogens such as Staphylococcus aureus, coagulase-negative staphylococci, enterococci, etc., as well as the pathophysiology of these infections.