The aim of this study was to give an overview about the epidemiological features of pneumococcal resistance in Hungary in the 1990s, and to assess the clinical relevance of drug resistance in Streptococcus pneumoniae primarily in upper respiratory tract infections and the role of risk factors in the acquisition of resistant strains. In Hungary, resistance in S. pneumoniae decreased slightly in recent years, but is still highly prevalent (around 40% to penicillin) compared to the prevalence in western and northern neighboring countries. The prevalent serogroup among resistant strains is 19A, as it was several years ago. In 76 case histories studies, chronic underlying diseases associated with long hospitalization, episodes of earlier hospitalization, and antibiotic therapy were found more frequently if the patient was infected with a resistant strain than with a susceptible one, indicating that these factors promote the acquisition of drug-resistant S. pneumoniae. Resistant S. pneumoniae modified the course of infection by prolonging the duration of hospitalization, making more courses of antibiotics necessary, including parenteral drugs, as well as more invasive interventions such as myringotomy and sinus puncture. These data justify the clinical relevance of resistance, particularly in the upper respiratory tract infections.