The tuberculosis (TB) epidemic is well controlled in most developed countries and the focus in these areas has shifted to TB eradication. Transmission within nonendemic areas is limited and most cases of TB result from reactivation of distant (latent) infection. With adequate resources, wide-scale use of preventive therapy can assist to eliminate the pool of latent infection that is required for TB eradication. In contrast, TB control remains poor in many developing countries, especially those worst affected by poverty and the human immunodeficiency virus (HIV) epidemic. In this review the authors critically assess the approach to TB preventive therapy in children and adults, focus on the underlying treatment rationale, discuss available data and identify issues of concern.