MUC1 is a membrane-bound mucin expressed on the apical surfaces of most mucosal epithelial cells. In normal lung epithelia, MUC1 is a binding site for Pseudomonas aeruginosa, an opportunistic human pathogen of great clinical importance. It has now been established that MUC1 also serves an anti-inflammatory role in the airways that is initiated late in the course of a bacterial infection and is mediated through inhibition of Toll-like receptor (TLR) signaling. MUC1 expression was initially shown to interfere with TLR5 signaling in response to P. aeruginosa flagellin, but has since been extended to other TLRs. These new findings point to an immunomodulatory role for MUC1 during P. aeruginosa lung infection, particularly during the resolution phase of inflammation. This review briefly summarizes the recent characterization of MUC1’s anti-inflammatory properties in both the respiratory tract and extrapulmonary tissues.