Toll-like receptors (TLRs) are evolutionarily conserved pattern-recognition molecules resembling the toll proteins that mediate antimicrobial responses in Drosophila. These proteins recognize different microbial products during infection and serve as an important link between the innate and adaptive immune responses. The TLRs act through adaptor molecules such as MyD88 and TIRAP to activate various kinases and transcription factors so the organism can respond to potential infection. TLR5 recognizes flagellin from both Gram-positive and Gram-negative bacteria and will cause the activation of NF-kappaB, leading to the activation of TNF-alpha and other cytokines. A common TLR5 stop codon polymorphism that disrupts TLR5 signaling is associated with susceptibility to Legionnaires’ disease and demonstrates the importance of TLR5 in the innate immune response.