The challenges ahead are not trivial: (i) the array of ligands for TLR2 may be larger than originally suspected, and its characterization may be an ongoing exercise as suggested by the evidence supporting their evolving nature; (ii) the relevance of various TLR2 ligands in the context of infection is not clear; and (iii) the tools used to study TLR2 activation both structurally and functionally are limited and may not recapitulate the full range of responses following TLR2 activation in vivo in response to bacteria. The gene discussed is TLR2; the disease is infection.