Although the number of people on treatment for HIV in the developing world is rapidly increasing, it is not clear what are the most effective and cost effective management strategies in resource-constrained settings. Regularly monitoring CD4 count and viral load are routinely done in the developed world, but their cost makes their use spotty in the developing world. We simulated the relative effectiveness and cost effectiveness of three management strategies based on clinical symptoms alone, CD4 monitoring, and viral load monitoring. Monitoring CD4 had an incremental lifetime cost of $73 and incremental effectiveness of nearly 1.5 years compared with symptoms alone. Monitoring viral load in addition to CD4 increased life expectancy by about 1 month at an increased lifetime cost of $1,250 per person. Managing patients with HIV based on CD4 cell counts is highly effective and cost effective. In resource-limited settings, it should be used in management of all patients with HIV before viral load monitoring is implemented.