QuantiFERON-TB Gold Plus (QFT-Plus) is the latest generation of interferon-gamma release assays (IGRAs) to receive approval from the US FDA, replacing its predecessor QuantiFERON-TB Gold In-Tube (QFT-GIT). The novelty of QFT-Plus is that it elicits a response from CD8 T-cells in addition to CD4 T-cells, thus collecting a broader response from T-cell subsets compared with QFT-GIT. It was developed with the aim to improve detection of M. tuberculosis infection (LTBI), especially among recently exposed, immunocompromised hosts and young children. In this mini review, we summarize the performance of QFT-Plus compared with QFT-GIT among active TB patients (a surrogate for LTBI), high-risk populations, and low-risk individuals based on recent publications. Studies comparing QFT-Plus to QFT-GIT currently do not support superior performance of QFT-Plus in individuals with active TB and LTBI. The difference in sensitivity between QFT-Plus and QFT-GIT in active TB patients was not significant in nearly all studies and ranged from -4.0 to 2.0%. Among high-risk groups, the agreement between QFT-Plus and QFT-GIT was 89.9 to 96.0% (kappa 0.80 to 0.91). The specificity in the low-risk population was slightly lower in QFT-Plus than QFT-GIT with a difference ranging from -7.4 to 0%. Further studies are needed to accurately evaluate the sensitivity of QFT-Plus in immunocompromised hosts and children. In addition, further evidence is required to validate a modified interpretation of QFT-Plus for the identification of false-positive results in low-risk healthcare workers.