The pneumococcus is the classic Gram-positive extracellular pathogen. The medical burden of diseases it causes is amongst the greatest in the world. Intense study for more than 100 years has yielded an understanding of fundamental aspects of its physiology, pathogenesis, and immunity. Efforts to control infection have led to the deployment of polysaccharide vaccines and an understanding of antibiotic resistance. The inflammatory response to pneumococci, one of the most potent in medicine, has revealed the double-edged sword of clearance of infection but at a cost of damage to host cells. In virtually every aspect of the infectious process, the pneumococcus has set the rules of the Gram-positive pathogenesis game.