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The epidemiology of non-typhoid Salmonella has changed significantly since the turn of the century. Interestingly, non-typhoid Salmonella epidemiology in Israel mirrors some important global trends, and these new trends are reviewed. Recent research that has shed more light on the true toll of non-typhoid Salmonella epidemic and resistance is also summarized.After more than three decades of a persistent rise, reports from Israel, the US, and the UK indicate that the trend may be reversed and the incidence of NTS illnesses is starting to decline. In contrast, the rates of resistance and multidrug resistance are increasing and expanding worldwide. Of major concern are the increasing rates of multidrug resistance in Salmonella typhimurium, particularly definitive phage-type 104, the alarming increase in low-level ciprofloxacin resistance among several non-typhoid Salmonella serotypes, and the upsurge of high-level ciprofloxacin resistance, mainly in Taiwan. In Israel, high rates of resistance were reported for Salmonella virchow, which accounts for 16% of non-typhoid Salmonella illnesses, and is highly invasive in children. The true burden of Salmonella illnesses in the US was calculated as 520 cases per 100 000, compared with an annual incidence of 13.4 per 100 000 of laboratory confirmed cases. Hospitalization and death rates were 20% and 0.6%, respectively. Infection with resistant non-typhoid Salmonella isolates, and particularly S. typhimurium, increases the likelihood of hospitalization and death.Many important trends of non-typhoid Salmonella epidemiology are not restricted to a single geographic location, but spread worldwide, reflecting the global nature of the epidemic. This epidemic imposes a heavy burden worldwide.