Synthetic oligodeoxynucleotides (ODNs) that contain immunostimulatory CpG motifs trigger an immunomodulatory cascade that involves B and T cells, natural killer cells and professional antigen-presenting cells. The response to CpG ODNs skews the host's immune milieu in favour of T helper 1 (T_H1)-cell responses and pro-inflammatory cytokine production — an effect that underlies their use as immunoprotective agents, vaccine adjuvants and anti-allergens. Preclinical studies provide evidence that CpG ODNs are effective for each of these uses. Ongoing clinical studies indicate that CpG ODN use is safe in humans, and that they modulate the immune response to co-administered allergens and vaccines.