Salmonella enterica is a bacterial zoonotic pathogen of global importance that cause approximately 80 million causes of foodborne illness each year.  Transmission dynamics of Salmonella from livestock to humans, from livestock to the environment and from the environment to humans are complex, and a systematic approach must be applied in order to reduce the burden of human salmonellosis.  A systematic approach to controlling salmonella in humans, animals and the environment has been developed using genomics-based approaches. This Syst-OMICS approach will be discussed with examples of how it is being applied to reduce the burden and duration of foodborne salmonellosis.