Purpose. Streptococcus pneumoniae is a commensal bacterium that normally colonizes the human nasopharyngeal cavity. Once disseminated, it can cause several diseases, ranging from non-invasive infections such as acute otitis media and sinusitis through to invasive infections with higher mortality, including meningitis and septicaemia. Since the identification of the first S. pneumoniae strain with decreased susceptibility to penicillin in the 1960s, antibiotic resistance among S. pneumoniae has increased disturbingly and the mechanisms of resistance have begun to unfold.Methodology. This work briefly reviewed the available data on the molecular mechanisms underlying antimicrobial resistance and its epidemiology among pneumococcal strains in Middle Eastern countries.Key findings. Both intrinsic and acquired mechanisms (mutations, acquisition of novel mobile genetic elements and sometimes gene duplication and overexpression) affect susceptibility to a large variety of antibiotics. In Middle Eastern countries, including Lebanon, Iran, Saudi Arabia and Turkey, surveillance showed a disturbing increase in the strength and prevalence of resistance to antibiotics over the years, especially in the last decade. However, no surveillance reports were found in other Middle Eastern countries, such as Syria and Iraq.Conclusion. In order to better survey, control and prevent the emergence of multidrug-and extremely drug-resistant S. pneumoniae strains, antimicrobial stewardship, national surveillance and public awareness programmes should be developed urgently in Middle Eastern countries.