Background: Shiga toxin-producing Escherichia coli infection is the most common cause of haemolytic uraemic syndrome in children – a form of thrombotic microangiopathy characterised by haemolysis, thrombocytopaenia, and acute kidney injury. In most cases, Shiga toxin-producing Escherichia coli-induced gastroenteritis is self-limiting; however, approximately 5–15% of patients develop haemolytic uraemic syndrome. Methods: Focused narrative review based on PubMed/MEDLINE searches covering the past 20 years, with emphasis on the last 5 years. Results and conclusions: The development of Shiga toxin-producing Escherichia coli and haemolytic uraemic syndrome in children results from gastrointestinal infection with Shiga toxin-producing bacteria, predominantly Escherichia coli, in combination with host susceptibility and modifiable clinical factors. Shiga toxin plays a central role in pathogenesis by binding to the Gb₃ receptor and inducing endothelial cell injury, leading to thrombotic microangiopathy. This process is further amplified by the inflammatory response and complement activation. The strongest determinants of severe disease and haemolytic uraemic syndrome development are strains producing Stx2, particularly specific subtypes, which exhibit increased cytotoxicity toward endothelial cells. Virulence factors that promote intestinal colonisation and attaching/effacing injury likely intensify mucosal damage and systemic toxin exposure. The risk of haemolytic uraemic syndrome is higher in younger children, possibly due to increased Gb₃ expression and immaturity of mechanisms regulating inflammation and complement activation. Available data also suggest a role for host genetic factors, particularly those related to complement regulation and endothelial function. Potentially modifiable clinical factors include delayed or insufficient hydration, as well as the use of antibiotics, antimotility agents, and nephrotoxic drugs, all of which may increase the risk of haemolytic uraemic syndrome.