In this chapter we will discuss the diagnosis and monitoring of individuals with HIV infection. The application and interpretation of these tests does not change dramatically when used in the immunocompromised host. The principal approach to the diagnosis of HIV infection involves serologic testing, although nucleic acid amplification tests play an important role in the diagnosis of acute HIV infection. The algorithm for diagnosis of HIV continues to evolve with newer assays that are able to detect infection within an earlier timeframe after HIV transmission. Viral load testing for HIV-1 is the cornerstone for monitoring patients on antiretroviral therapy. Genotypic and phenotypic resistance tests are employed when antiretroviral resistance is suspected and results help guide therapy. The tropism assay must be performed to determine the efficacy of CCR5 chemokine receptor antagonists. Next-generation sequencing methods are an innovative approach to assessing archived antiretroviral resistance in patients with virologic suppression. The success of antiretroviral therapy with improved long-term outcomes has made transplantation in HIV-infected patients a reality.