Streptococcus pneumoniae is one of the major human bacterial pathogens. Current prophylactic agents against this pathogen are limited in their protective abilities and the role of therapeutics has been inadequate as resistant strains emerge. The development of new and improved therapies to combat the pneumococcal disease is necessary. In order to accomplish this, an understanding of the interactions between this bacterium and the host tissues is essential. Such interactions largely involve extracellular virulence factors that are expressed by the pathogen to interact with the host. These virulence factors include those based on sugars (glycome-based) as their building blocks, and proteins that are built from amino acids (proteome-based). The first group includes primarily the capsule, teichoic and lipoteichoic acids. The second group is diverse and includes numerous surface proteins that are attached to the cell wall of pneumococci utilizing a variety of methods. For the purpose of this review these surface proteins were divided into three categories, proteins bound to peptidoglycan, those bound to choline residues present on the surface of penumococci, and those bound to the lipids of the cytoplasmic membrane. Both the glycome-based and protein-based virulence factors are described, analyzed, and represented graphically. Whenever possible, structural properties of these molecules were introduced.