OBJECTIVE This review will describe advances in detection and results of monitoring persistent viremia in patients on long-term suppressive therapy. In addition, the review explores the usefulness of these methods in determining the effectiveness of new HIV-1 eradication strategies in purging persistent HIV-1 reservoirs. RESULTS Quantification of plasma HIV-1 RNA levels remains essential for determining the success of combination antiretroviral therapy (cART) in treated patients. Recently, several new platforms with improved sensitivity for quantifying HIV-1 RNA have been developed and the application of these assays has revealed that low-level viremia persists in patients on suppressive therapy. In addition, new technological advances such as digital PCR have been proposed to increase the sensitivity of measuring and characterizing persistent HIV-1 viremia. The application of these assays will be important in determining the effectiveness of future HIV-1 eradication strategies. CONCLUSIONS The level of HIV-1 RNA in patient plasma remains an important marker for determining the success of cART. New sensitive assays have found that HIV-1 persists in the plasma of patients on suppressive therapy that may have implications for the clinical management of this disease and strategies for eliminating HIV-1 infection.