Most eubacteria are sensitive to penicillin because the antibiotic inhibits synthesis of peptidoglycan, an essential constituent of their cell walls. A few eubacteria have no measurable peptidoglycan, and, with one exception, they are not susceptible to penicillin. The exception is the genus Chlamydia whose members are just as sensitive to penicillin as peptidoglycan-containing bacteria. A numbers of ways to resolve this anomaly, penicillin sensitivity without peptidoglycan, are proposed. It is concluded that there are serious objections to each one and that the chlamydial anomaly remains unresolved. However, examination of the relation between penicillin and chlamydiae is useful because it reveals how little is known of the evolutionary history of penicillin, penicillin-binding proteins, and peptidoglycan.