**Abstract**

Non-typhoidal *Salmonellae* (NTS) belong to *Salmonella enterica* subspecies *enterica* and are common causes of foodborne illnesses in humans. Diarrhea is a common symptom but infection occasionally results in life-threatening systemic involvement. One member of the group, *S. enterica* subspecies *enterica* serovar Typhimurium has been extensively studied in live animal models particularly mice and cattle, leading to a better understanding of the pathogenesis of NTS and the development of diarrhea, respectively. This comprehensive review provides an insight into the genetic regulation of over 200 virulence determinants and their involvement in the four steps of *Salmonella* pathogenesis, namely: attachment, invasion, macrophage survival and replication, and systemic dissemination. There is, however, a paucity of information on the functions of some virulence factors present on the *Salmonella* pathogenicity islands (SPIs). The emergence of next generation sequencing (NGS) technology and the availability of more bacterial genomes should provide further insights into the biology of virulence determinants, mechanisms of NTS pathogenesis and host adaptation of *Salmonella*. The new knowledge should translate into improvement and innovations in food safety, and control of salmonellosis as well as better understanding of zoonotic infections in the context of One Health capturing the risks to humans, animals and the environment.

**Keywords:** non-typhoidal *Salmonellae*, virulence determinants, Typhimurium, attachment, intracellular survival, systemic dissemination, NGS, food safety, *Salmonella* pathogenicity islands, SPI
