SP-A and SP-D contribute to host defense against respiratory viral infection. The most extensive body of evidence relates to influenza A viruses (IAV), and evidence from gene-deleted mice also indicate a role for surfactant collectins in defense against respiratory syncytial virus (RSV) and adenovirus. Some important respiratory pathogens including rhinovirus and metapneumovirus have not yet been examined. Viral pathogens that enter the body via the respiratory tract (e.g., Ebola virus), replicate in the lung (e.g., human immunodeficiency virus or HIV) or infect the lung in immuno-compromised hosts (e.g., herpes simplex virus or HSV) are inhibited by collectins. SP-A and SP-D are expressed in other mucosal surfaces (e.g., the eye or genitourinary tract) where they may play roles in antiviral defense. In addition to direct antiviral activities, the SP-A and SP-D modulate innate and adaptive immunity and inflammation associated with infection. The relative importance of antiviral vs anti-inflammatory effects of SP-A and SP-D in viral infections and the potential use of these collectins as therapeutics for viral infections are under investigation.