Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. It is a major health concern and causes substantial morbidity and mortality. It is imperative that the signs of sepsis are identified early in both adult and paediatric patients and appropriately escalated to initiate early treatment and improve prognosis. This paper aims to discuss the change in classification from the previous systemic inflammatory response syndrome (SIRS) criteria to the current definition in adults and also the unchanged definition in children. The hallmark signs of sepsis (both red and amber flags) are discussed in relation to their underlying cellular mechanisms to provide a comprehensive overview for clinicians in primary care, hospital and community settings. The rise of antimicrobial resistance is also an increasing global health concern with resistant bacteria from common infections likely to result in greater patient morbidity and worse outcomes.A literature search identified reported sepsis cases in dentistry through searches in Ovid Medline and Embase from January 1990 to December 2019. Only primary studies were included with no restrictions on languages. Four articles were identified which reported sepsis associated with tooth extractions, dental abscess and submental/submandibular cellulitis. It is well known that locoregional infections of dental origin have the potential to cause sepsis. Therefore, dental healthcare professionals need to be vigilant and understand the specific signs and escalation protocols to ensure patient safety.