Leptospirosis, an emerging infectious disease, is a worldwide zoonosis of human and veterinary concern. Caused by pathogenic spirochaetes of the genus Leptospira, the disease presents greater incidence in tropical and subtropical regions. Humans can be infected by exposure to chronically infected animals and their environment. The genome sequence of Leptospira interrogans serovar Copenhageni was recently reported. It contains a broad array of genes encoding for regulatory system, signal transduction, and methyl-accepting chemotaxis proteins, conforming to the organism's ability to respond to diverse environmental stimuli. A large number of exported lipoproteins and transmembrane outer membrane proteins were identified that may be involved in leptospiral pathogenesis and protective immunity. Comparative analysis with the Leptospira interrogans serovar Lai genome revealed that, despite genetic similarity, there are structural differences, including a large chromosomal inversion. The leptospiral genome sequence, combined with bioinformatics tools, offered a unique opportunity to search for immune targets to be used for vaccine or diagnostic kit development. Out of a hundred recombinant proteins tested, sixteen were recognized by antibodies present in sera from patients diagnosed with leptospirosis and might be useful for these purposes. The most important results obtained within genome sequences, comparative genomics, and outer membrane genome-derived protein expressed in E. coli are reviewed here.