The C-type lectin family comprises a large set of proteins that are structurally evolved to gain functional diversification from ancient proteins following multiple gene duplication events. On the basis of the amino acid alignment analysis, the C-type lectin members have been classified into 17 groups. The group V C-type lectin receptors (CLRs) are further enriched in two clusters, i.e., the Dectin-1 cluster and the Dectin-2 cluster; in mouse, the former cluster includes Clec12a, Clec-2, Clec12b, Clec9a, Clec-1, Dectin-1 and Lox-1, and the latter includes Dcir1-4, Dcar1,2, Dectin-2, Mcl and Mincle. The CLRs are type II transmembrane proteins consisting of a single extracellular C-type lectin domain (CTLD), a stalk region and a distinct intracellular region. These receptors are predominantly expressed in innate immune cells where they function as pattern recognition receptors (PRRs) through recognition of pathogen-associated molecular patterns (PAMPs). Upon PAMP-sensing through CTLD(s), CLRs induce activation of innate immune responses such as phagocytosis, cytokine/chemokine secretion, ROS production and shaping of adaptive immune responses. Therefore, it is important to elucidate microbial recognition of CLRs in relation to host immune functions. In this study, we report molecular recognition of murine CLRs and the extensive involvement of the CLRs in microbial infection.