Tuberculosis (TB) has once again become a major public health threat owing to the combined effects of deteriorating socioeconomic situations and the emergence of the HIV/AIDS pandemic. The only vaccine available against TB, although effective in reducing the burden of childhood TB, shows enormous variability in its efficacy against pulmonary TB, which is the most common form of the disease in adults. Most areas of high TB incidence and poor TB vaccine efficacy have a high prevalence of intestinal helminth infections. Such infections have been shown to cause a range of immunomodulation characterized by enhanced T helper 2-type cytokine profile, high immunoglobulin E levels and upregulated regulatory T-cell activity, as well as chronic immune activation. An altered background immune profile could have adverse effects on the outcome of subsequent infections and vaccinations. In support of this hypothesis, studies conducted in animals and humans living in worm-endemic areas have shown that helminths impair resistance against a number of infections of major public health importance, including TB, malaria and HIV/AIDS. Understanding such interactions could assist in the design of vaccines against these diseases.