The dynamics of HIV-1 viremia is a complex and evolving landscape with clinical and epidemiological (public health) implications. Most studies have relied on the use of set-point viral load (VL) as a readily available proxy of viral dynamics to assess host and viral correlates. This review highlights recent findings from population-based studies of set-point VL, focusing primarily on robust data related to host genetics. A comprehensive understanding of viral dynamics will clearly need to consider both host and viral characteristics, with close attention to (i) the timing of VL measurements, (ii) the biology of viral evolution, (iii) compartments of active viral replication, (iv) the transmission source partner as the immediate past microenvironment, and (v) proper application of statistical models. © 2012 by the authors; licensee MDPI, Basel, Switzerland.