Toll-like receptors (TLRs) have been recognized to play a fundamental role in the recognition of microbial pathogens and the activation of innate immunity. However, it has also turned out that triggering of TLRs with purified compounds or synthetic ligands represents a powerful means to modulate innate as well as adaptive immune responses. Among the substances currently under investigation as immune response modifiers CpG-DNA has gained particular interest. One reason for this is the feasibility to easily synthesize and modify immunostimulatory CpG-containing oligodeoxynucleotides (CpG-ODNs). This review deals with the structural needs of CpG-ODNs. CpG-ODNs are discussed as being composed of distinct building blocks (e.g. sequence strings, backbone modifications) giving rise to a concept of structural modules within CpG-ODNs.