Since the first case reported in 1981, more than 60 million individuals have succumbed to HIV worldwide. Although great efforts have been put forth in developing therapeutic drugs and effective vaccines for the treatment and prevention of HIV infection, these efforts are not correlated to the reported case of cured HIV infection. The first case of cured HIV infection, from allogenic stem cell transplantation, may shed light on future prevention and therapy of HIV infection. The choice of gene target, however, must first be evaluated regarding stem cell based gene therapy for HIV infection. Out of the tens of genes that had shown anti-HIV infection potentials, CCR5 was described to be effective in stem cell based gene therapy in 2005. Here, we appreciate the clinical observations that directly led to the choice of CCR5, rather than other genes for stem cell gene therapy.