The MICs of 24 antimicrobials for 26 Leptospira spp. serovars were determined using a broth microdilution technique. The MICs at which 90% of isolates tested were inhibited (MIC90s) of cefepime, imipenem-cilastatin, erythromycin, clarithromycin, and telithromycin were all ≤0.01 μg/ml. The MIC90s of amoxicillin, aztreonam, cefdinir, chloramphenicol, and penicillin G were ≥3.13 μg/ml. Many antimicrobials have excellent in vitro activity against Leptospira.