Ninety years after the discovery of pneumococcal Transformation, and 74 years after the work of Avery and colleagues that identified DNA as the genetic material, Streptococcus pneumoniae is still one of the most important model organism to understand Bacterial Genetics and Genomics. In this Chapter special emphasis has been given to Genomics and to Mobile Genetic Elements (the Mobilome) which greatly contribute to the dynamic variation of pneumococcal genomes by horizontal gene transfer. Other topics include molecular mechanisms of Genetic Transformation, Restriction/Modification Systems, Mismatch DNA Repair, and techniques for construction of genetically engineered pneumococcal strains.