HACEK group organisms are very fastidious organisms (Haemophilus spp., Actinobacillus actinomycetemcomitans, Cardiobacterium hominus, Eikenella corrodens, Kingella spp.) that can produce serious invasive infections such as endocarditis. Problems with susceptibility testing methods and their rarity of isolation limit available information of therapeutic choices, particularly among newer antimicrobial agents. Forty-two HACEK strains were tested by the Etest (AB BIODISK, Solna, Sweden) method against 29 antimicrobial agents. Nearly all compounds exhibited activity with best potency observed among the tested beta-lactamase inhibitor combinations, "third- or fourth-generation" cephems, meropenem, fluoroquinolones, and rifampin. Numerous therapeutic options appear possible for initial parenteral treatment followed by oral "step-down" or switch therapy. Each case of HACEK infection therapy should be guided by accurate susceptibility tests, for which the Etest seems preferred for these fastidious species.