Group A beta-haemolytic streptococci (GAS) have remained sensitive to penicillin, but penicillin V therapy does not eradicate GAS in 5-30% of cases of GAS tonsillitis. Multiple factors contribute to treatment failure, the foremost among these being lack of compliance with the prescribed therapy, tolerance of GAS towards the killing effect of penicillin, inactivation of penicillin by bacterial beta-lactamases, and absence of bacteriocin-producing non-haemolytic streptococci from the oral flora. The effect of local immunity should be further assessed. It is unlikely that environmental sources of GAS play any significant role. Throat cultures should not routinely be repeated after penicillin treatment. If, in special cases, a new course of treatment is indicated, penicillin V should still be preferred. In the light of modern pharmacological insights, multiple dosing schedules may be desirable in the therapy of GAS tonsillitis.