The current literature is controversial in providing evidence to determine the optimal time to initiate therapy among patients with HIV. However, there is evidence that initiating early treatment might provide benefits by treating primary HIV infection, preserving normal immune function, suppressing HIV viral replication, deferring clinical progression, and reducing HIV transmission. The biggest challenges in initiating treatment early are issues related with long-term management, including toxicities, adherence, and drug resistance. However, the availability of superior new antiretroviral drugs and simplified regimens, the development of effective treatment strategy, and further improvement of adherence through directly observed treatment are addressing the issues and changing the balance towards earlier treatment.