During the past decade and a half, quantitation of plasma-associated human immunodeficiency virus type 1 (HIV-1) RNA level, or HIV-1 load, has been validated in clinical practice and clinical trials as an important surrogate marker of HIV-1 disease progression and of the potency and durability of antiretroviral regimens. This review highlights some of the history, accomplishments, and impact of Tom Merigan's laboratory on the use of HIV-1 load as a marker, as well as on updating technologies for determining HIV-1 load, their performance, interpretation of the results, and their use in clinical practice.