The occurrence of lipodystrophy in patients taking antihuman immunodeficiency virus(HIV) medications is a serious problem as it is irreversible even after drug withdrawal. Although it was first recognized in patients taking proteinase inhibitors, other types of anti-HIV agents can also cause lipodystrophy. In a recent publication by Jones et al entitled “Highly active antiretroviral therapy dysregulates proliferation and differentiation of human pre-adipocytes” in World Journal of Virology, it was reported that simultaneous treatment of human subcutaneous adipocytes with anti-HIV drugs with different mechanisms of action synergistically exerted antiadipogenesis effects in vitro, warning us to take utmost care in every case receiving combination antiretroviral therapy(cART). For elucidation of the molecular basis for cART-related lipodystrophy, multi-faceted approaches should be taken, based on a deeper understanding of the development and organization of adipose tissues. The occurrence of lipodystrophy in patients taking antihuman immunodeficiency virus (HIV) medications is a serious problem as it is irreversible even after drug withdrawal inhibitors. Other types of anti-HIV agents can also cause lipodystrophy. In a recent publication by Jones et al entitled “Highly active antiretroviral therapy dysregulates proliferation and differentiation of human pre-adipocytes ” in World Journal of Virology, it was reported that simultaneous treatment of human subcutaneous adipocytes with anti-HIV drugs with different mechanisms of action synergistically exerted antiadipogenesis effects in vitro, warning us to take utmost care in every case receiving combination antiretroviral therapy (cART). For elucidation of the molecular basis for cART-related lipodystrophy, multi-faceted approaches should be taken, based on deeper understanding of the development and organization of adipose tissues.