Two cases of bacterial endocarditis in children, caused by viridans group Streptococcus which requires vitamin B6 or thiol compounds for growth are reported. It is important to recognize these organisms as a possible cause of endocarditis because supplemented media are needed for their isolation and sensitivity testing. These organisms may be penicillin-sensitive, -resistant, or -tolerant. An organism is considered tolerant to an antibiotic when the minimum bactericidal concentration of that antibiotic is ≥32 times the minimum inhibitory concentration. One of our patients relapsed when treated with a single antibiotic to which the B6-dependent viridans group Streptococcus was tolerant. If a B6-dependent viridans group Streptococcus is isolated from a patient with endocarditis, therapy should be initiated with penicillin and an aminoglycoside until sensitivities are available. Sensitity testing should include both the MIC and MBC and adequate therapy can be confirmed by determining the serum bactericidal activity.