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<i>Background and Objectives:</i> <i>Helicobacter pylori</i> (<i>H. pylori</i>) infection is common worldwide and may cause gastroduodenal complications, including cancer. In this review, we examine the prevalence and distribution of various <i>H. pylori</i> genotypes and the risk factors for <i>H. pylori</i> infection, particularly in the Middle East and North Africa (MENA) region. We also introduce different global screening methods and guidelines and compare them to those currently in use in the MENA region. <i>Materials and Methods:</i> We searched the Google Scholar, PubMed, and Saudi Digital Library (SDL) databases for clinical trials and articles published in English. The data collection was mainly focused on MENA countries. However, for <i>H. pylori</i> genotypes and diagnostic methods, studies conducted in other regions or reporting global practices and guidelines were also included to allow a comparison with those in the MENA region. We also included studies examining the prevalence of <i>H. pylori</i> infection in healthy participants. <i>Results:</i> <i>H. pylori</i> infection is highly prevalent in the MENA region, mainly because of the accumulation of risk factors in developing countries. Herein, we highlight a lack of good quality studies on the prevalence of various <i>H. pylori</i> genotypes in the MENA region as well as a need for standard diagnostic methods and screening guidelines. Due to the complications associated with <i>H. pylori</i>, we recommend routine screening for <i>H. pylori</i> infection in all gastroenterology patients admitted in the MENA region. <i>Conclusion:</i> Concerted effort will first be required to validate affordable, non-invasive, and accurate diagnostic methods and to establish local guidelines with adapted cut-off values for the interpretation of the test results.