Hepatitis B virus occurs among the ubiquitous viral pathogens that pose a serious threat to the lives of millions around the globe. As a consequence of lacking proofreading during the replication cycle directed by the reverse transcriptase, HBV became distinguished by a considerable genetic variation. To date, ten different genotypes of this virus have been recognized through our world. Each of these genotypes was linked to various rates of severity and disease outcomes, ranging from cirrhosis to liver carcinoma, and to response to antivirals as well. Therefore, genotypic studies and molecular characterization of the virus may offer unparalleled assistance to predict the most successful treatment approaches. Moreover, this review attempts to clarify some aspects of the HBV molecular biology and to provide an updated insight to genetic variations through collecting of the most recent or available studies by web searching engines conducted in several countries of the Middle East. Thus, it has been noted that the dominant genotype of HBV in several cities in Iraq as well as Middle Eastern regions was represented by genotype D (96.8% & 90%, respectively). However, other local studies showed considerable elevation in the rate of mixed infections, where the most frequent mixtures were composed of 3 and 2 genotypes represented by 35.1 and 29.7%, respectively.