The recent emergence of hypervirulent strains of Clostridium difficile and their ability to spread across continents, has caused alarm in both hospitals and the community. This has drawn attention away from other important pathogenic C. difficile strains, which are responsible for significant morbidity and mortality. Little is known about the genetic diversity of these strains and their less pathogenic counterparts. The recent publication of the genome sequence of strain 630 and advances in both microarray and mutagenesis technologies promises to revolutionise our understanding of the pathogenesis and population dynamics of C. difficile. This chapter summarises the salient findings of the 630 genome sequence and includes phylogenetic analysis of C. difficile strains from diverse origins.