Childhood TB is difficult to diagnose, since disease tends to be paucibacillary and sputum specimens are not easy to obtain in children. Thus, blood-based immune assays are an attractive option. Systematic reviews of serological assays suggest that these tests produce highly inconsistent estimates of sensitivity and specificity, but much of the serology literature is based on adults. In children, there is insufficient evidence to recommend the use of serological tests for active TB diagnosis. Interferon-gamma release assays (IGRA) do not offer substantial improvements in sensitivity over the TST for the diagnosis of active disease. For latent TB infection, the IGRA correlates well with the exposure gradient and seems to have utility in reducing the number of children who undergo preventive therapy due to false-positive TST. Although IGRAs can be used as evidence of TB infection in children, appropriate specimen collection and microbiological confirmation of TB disease should remain a priority.