Immune reconstitution following organ transplantation is absolutely critical in preventing infectious complications. However, understanding the kinetics of immune reconstitution and its potential impact on the clinical management of transplant patients remains a significant challenge. Over the last decade, various platform technologies have emerged which have provided important insights into the immune reconstitution kinetics in transplant patients. However, many of these technologies are too complicated and cumbersome to implement in a clinical setting. In this issue of the Journal of Clinical Microbiology , A Chiereghin et al. (J Clin Microbiol xx:xxxx-xxxx, 2018, https://doi.org/10.1128/JCM.01040-17) report the results of their evaluation of the QuantiFERON®-CMV (QFN®-CMV) assay to assess human cytomegalovirus (CMV)-specific CD8+ T-cell immunity in heart transplant recipients as a prognostic tool. These studies showed that patients with absence of global immune reactivity in the QFN®-CMV assay were at a higher risk of developing CMV after discontinuing antiviral prophylaxis. Furthermore, failure to reconstitute CMV-specific immunity after resolution of the first episode of viremia was associated with viral relapse. These observations, along with other recent clinical studies utilizing the QFN®-CMV assay, demonstrate that systematic monitoring of antiviral immunity can be successfully used as a prognostic tool and also to guide changes to the clinical management of transplant patients.