The acronym HACEK describes a heterogeneous group of organisms that share three major characteristics. First, they are small gram-negative rods that are commonly present as part of normal oral–pharyngeal or respiratory flora. Second, they are fastidious microorganisms that require special culture media. Third, they have a predilection to infect heart valves. The HACEK group includes Haemophilus species (except Haemophilus influenzae), Actinobacillus actinomycetemcomitans, Cardiobacterium hominus, Eikenella corrodens, and Kingella species. These organisms are infamous for their ability to cause endocarditis although, rarely, they can also cause a variety of other infections (Table 135.1). For example, human bites can result in cellulitis or abscess formation resulting from HACEK organisms, especially Eikenella species, and various Haemophilus species can cause epiglottitis or brain abscesses. Members of the HACEK group are normal indigenous flora of the oral cavity. Systemic hematogenous spread may occur after dental manipulation or secondary to periodontal disease. Thereafter, individuals with underlying valvular heart disease are at risk of developing endocarditis. Antibiotic prophylaxis before dental manipulation does not ensure complete prevention against these fastidious organisms. However, the risk of endocarditis is very small after dental manipulation, even in patients with significant valvular disease. Millions of patients undergo dental procedures annually, yet the cases of infective endocarditis (IE) caused by HACEK group organisms are rare.