The treatment of children with TB is influenced by a number of factors specific to both the bacterium and the child. We review the variables impacting the selection of individual medications; indications, pharmacology, dosing and side effects for first- and second-line agents; adjunctive therapy; and special cases, including treatment of TB in HIV-infected children and multidrug-resistant TB. Finally, evolving trends in TB therapy, such as the impact of HIV and multidrug-resistant TB on future therapeutics, emerging or re-emerging medication options, shorter-course regimens and immunomodulation, are discussed.