Salmonella enterica is a facultative intracellular pathogen of worldwide importance. Infections may present in a variety of ways, from asymptomatic colonization to inflammatory diarrhoea or typhoid fever depending on serovar- and host-specific factors. Human diarrhoeal infections are frequently acquired via the food chain and farm environment by virtue of the ability of selected non-typhoidal serovars to colonize the intestines of food-producing animals and contaminate the avian reproductive tract and egg. Colonization of reservoir hosts often occurs in the absence of clinical symptoms; however, some S. enterica serovars threaten animal health owing to their ability to cause acute enteritis or translocate from the intestines to other organs causing fever, septicaemia and abortion. Despite the availability of complete genome sequences of isolates representing several serovars, the molecular mechanisms underlying Salmonella colonization, pathogenesis and transmission in reservoir hosts remain ill-defined. Here we review current knowledge of the bacterial factors influencing colonization of food-producing animals by Salmonella and the basis of host range, differential virulence and zoonotic potential.