Streptococcal adhesion, invasion, intracellular trafficking, dissemination, and persistence in eukaryotic cells have a variety of implications in the infection pathogenesis. While cell adhesion establishes the initial host contact, adhering bacteria exploit the host cell for their own benefit. Internalization into the host cell is an essential step for bacterial survival and subsequent dissemination and persistence, thus playing a key role in the course of infection. This chapter summarizes the current knowledge about the diverse mechanisms of streptococcal adhesion to and invasion into different eukaryotic cells and the impact on dissemination and persistence which is reflected by consequences for the pathogenesis of streptococcal infections.