Research on Streptococcus pneumoniae has revealed key aspects in the study of infectious diseases and pathogen evolution, but pneumococci remain a major cause of morbidity and mortality. New insights into the pathogenic mechanisms of this species confirmed the key role of the capsular polysaccharide but have also identified the important functions played by proteins in the interaction with the host. The capacity of pneumococci to exchange DNA is central in the adaptation to human-imposed selective pressures and our understanding of the mechanisms underlying competence is raising new questions about the evolution of these bacteria. A greater knowledge of the biology of pneumococci resulted in new diagnostic tests that together with a revision of the breakpoints defining resistance to penicillin and the advent of conjugate vaccines, are changing our understanding of the burden of pneumococcal disease and our approaches to prevent and treat infections by this important pathogen.