Salmonella infections are endemic in sub-Saharan Africa (SSA). They can be divided into typhoidal (caused by Salmonella Typhi and S. Paratyphi A) and non-typhoidal Salmonella (NTS) (i.e. S. Typhimurium and S. Enteritidis) and are amongst the leading cause of invasive bloodstream infections in Africa. In 2017, it was estimated that there were 535 000 cases of invasive non-typhoidal Salmonella (iNTS) disease, and 14.3 million cases of typhoid and paratyphoid fever globally (see Fig. 26.1). Whilst typhoid is responsible for a greater number of infections, iNTS disease is more commonly a severe illness. iNTS disease is a neglected tropical disease commonly seen in individuals with underlying risk factors (age, malnutrition, malaria, sickle cell disease and HIV). Blood culture is the gold standard for diagnosis for invasive bloodstream Salmonella infections, but due to limitations in diagnostic capacity in Africa, diagnosis of invasive Salmonella infection is frequently made on clinical grounds in febrile patients. Emergence of antimicrobial resistance (AMR) has made clinical management more challenging and is a major public health concern.