Penicillin-resistant Streptococcus pneumoniae was first described in South Africa in 1977 and soon afterward was reported in other countries and in Japan. According to NCCLS standards for antimicrobial susceptibility tests, in vitro activity of S. pneumoniae is the best procedure using the minimum inhibitory concentration method. Benzylpenicillin, cefotaxime or ceftriaxone, and meropenem should be tested by a reliable MIC method and the susceptibility should be reported in the case isolated from blood and/or cerebrospinal fluid. Using the oxacillin test, it is difficult to distinguish penicillin-resistant from intermediate strains or sometimes susceptible strains.