HLA-Ghas a relevant role in immune response regulation. The overall structure of theHLA-Gcoding region has been maintained during the evolution process, in which most of its variable sites are synonymous mutations or coincide with introns, preserving major functionalHLA-Gproperties. TheHLA-Gpromoter region is different from the classical class I promoters, mainly because (i) it lacks regulatory responsive elements for IFN-γand NF-κB, (ii) the proximal promoter region (within 200 bases from the first translated ATG) does not mediate transactivation by the principal HLA class I transactivation mechanisms, and (iii) the presence of identified alternative regulatory elements (heat shock, progesterone and hypoxia-responsive elements) and unidentified responsive elements for IL-10, glucocorticoids, and other transcription factors is evident. At least three variable sites in the 3′ untranslated region have been studied that may influenceHLA-Gexpression by modifying mRNA stability or microRNA binding sites, including the 14-base pair insertion/deletion, +3142C/G and +3187A/G polymorphisms. Other polymorphic sites have been described, but there are no functional studies on them. TheHLA-Gcoding region polymorphisms might influence isoform production and at least two null alleles with premature stop codons have been described. We reviewed the structure of theHLA-Gpromoter region and its implication in transcriptional gene control, the structure of theHLA-G3′UTR and the major actors of the posttranscriptional gene control, and, finally, the presence of regulatory elements in the coding region.