Ethanol suppresses innate resistance to a variety of microbes, and findings of studies from both our laboratory and other laboratories indicate suppression of responses is mediated through two Toll-like receptors (TLRs): TLR3 and TLR4. In this article, we review recent findings from studies in our laboratory, indicating that ethanol also suppresses responses mediated through other TLRs. Considering the importance of TLR-mediated responses in innate immunity, this supports the possibility that suppression of these responses may constitute a major mechanism by which ethanol suppresses innate immunity. In addition, ethanol-induced changes in cellular signaling and in patterns of gene expression induced through TLR3 were examined in mouse peritoneal macrophages, and these results are reviewed in this article. Signaling through TLR3 was inhibited, and results of DNA microarray analysis supported the notion that inhibition of an interferon-related amplification loop might be responsible for suppression of gene expression for several effector molecules of innate immunity and inflammation not previously known to be altered by ethanol. Thus, ethanol alters responses through most or all mouse TLRs, and this suppresses expression of a wide range of innate immune mediators.