Salmonella spp. represent one of the most common causes of bacterial foodborne illnesses around the world. The species Salmonella enterica contains more than 2500 serotypes, and emergence of new human pathogenic Salmonella strains and serotypes represents a major public health issue. Salmonella enterica subsp. enterica serotype 4,5,12:i:- represents a monophasic variant of Salmonella Typhimurium, which has rarely been identified before the mid-1990s. The prevalence of this serotype among human salmonellosis cases has increased considerably since the mid-1990s and Salmonella 4,5,12:i:- currently (i. e., the first decade of the 2000s) represents one of the most common serotypes among human cases in many countries around the world. This paper discusses our current knowledge of the global ecology, epidemiology, transmission, and evolution of this emerging Salmonella serotype.