Penicillin resistance in Streptococcus pneumoniae, which has been occasionally described in European isolates since the early 1970s, presently constitutes a general problem, although its rate may vary largely between countries and areas. Spain and Hungary show the highest rates of resistance and were probably the starting point for further dissemination to adjacent and distant countries. In Europe, resistant strains belong predominantly to serotypes 6, 9, 14, 19, and 23, and are isolated more frequently from pediatric than from adult patients, and from respiratory and CSF samples rather than blood. Although penicillin resistance in pneumococci is usually a well-recognized problem, some difficulties, mainly related to methodologic aspects of in vitro susceptibility testing, still subsist for its proper surveillance, but may be overcome through the adoption of adequate diagnostic protocols and tools.