Successful resolution of leptospirosis in cattle by administration of dihydrostreptomycin-penicillin G confirms results obtained by other investigators. Three other antibiotics (oxytetracycline, tilmicosin, and ceftiofur) also were effective for resolving leptospirosis and may be useful substitutes for dihydrostreptomycin, an antibiotic that is no longer available for use in food-producing animals in the United States. Cost, safety, and withdrawal times of these various treatment options need to be considered.