Non-typhoidal Salmonellae are a major cause of infectious diarrhoea worldwide and can cause invasive diseases, including bacteraemia, meningitis and osteomyelitis. Young or immunocompromised children and those with underlying conditions such as sickle cell disease are particularly vulnerable to invasive disease. There has been an increase in the rate of resistant non-typhoidal Salmonella, which is associated with invasive disease and hospitalisation. The intracellular nature of non-typhoidal Salmonella protects against extracellular antibiotics and can facilitate disease relapse, particularly meningitis. Effective antimicrobial agents with good intracellular penetration include azithromycin, fluoroquinolones and third-generation cephalosporins. Antibiotic treatment of non-typhoidal Salmonella gastroenteritis is only indicated if there are risk factors for invasive disease as it can prolong excretion and does not shorten the duration of gastrointestinal symptoms. Optimal choice and length of therapy for gastroenteritis and invasive disease in children is not clear. Here, we provide a review of the literature and treatment recommendations.