Access and well-modulated use of antiretroviral agents (ARVs) in North America dates as early as 1990 with the initial guidelines recommended zidovudine monotherapy, just 4 years after FDA approved the drug. Continued review of emerging data, led to the recommendation of highly active antiretroviral treatment (HAART) in 1998. Clear documentation of access and use of antiretroviral therapy (ART) in resource limited settings was first observed in 2002 after the World Health Organization (WHO) issued guidelines for resource limited settings, and included key ARVs into the WHO essential drug list. Delayed access to ART heavily impacted the initial control of the HIV epidemic in resource limited settings, but even with improved access to ART, differences in the management of HIV still exist; including timing for ART initiation and HIV/ART monitoring strategies. Access to key HIV/ART monitoring tools including viral load testing is limited in low resource settings, leading to gaps in HIV/ART management that may no longer be experienced in resource rich settings. Geographical variations in HIV sub-types and key co-infections further subject the control and management of HIV to demographic influence. Until now, resource availability and demographic differences are key determinants in treatment initiation and regimen selection, while variable access to ART and key monitoring tools possibly affect the HIV epidemic, making its control less effective in some settings.