Brucellosis is a debilitating and incapacitating bacterial disease that affects all livestock species and wildlife. Despite the fact that the disease has been eradicated from many countries, it still causes public health concerns and economic losses in animal productions, particularly in the Mediterranean countries. In the last few years, brucellosis has reemerged as a new challenge with new foci of disease, both in humans and animals. Brucellae have been isolated from wildlife, carrier hosts and non-classical hosts. However, little information is available on the role of environment and wildlife in transmission and dissemination of the infection. Moreover, the risk for livestock and humans infection concerning wildlife and carrier hosts’ contact and environmental contamination cannot be assessed. Tackling this disease will improve animal health and productivity and bolsters the economies. Several aspects of its biology, host/pathogen interaction and virulence mechanisms are not understood yet. To explain its epidemiology, virulence mechanisms and host specificity, a better understanding of Omics (genomics, transcriptomics, proteomics and metabolomics) of brucellae will be needed. To date, few multicenter projects have been conducted on genomics and proteomics of Brucella and this kind of approach is paramount to tackle this dangerous disease.