The fine-tuning of the innate immune response by microRNAs (miRNAs) is a concept now supported by a rapidly growing body of evidence. Target prediction analyses indicate that up to a half of innate immune genes could be under the direct regulation of miRNAs. However, the extent to which miRNAs regulate innate immunity remains poorly defined and is currently limited to a handful of target genes. This review highlights several important parameters of miRNA regulation, mostly neglected in the field, which underpin the relevance of miRNAs in the regulation of innate immunity.