Signalling C-type lectin receptors (CLRs) are crucial in shaping the immune response to fungal pathogens, but comparably little is known about the role of these receptors in bacterial, viral and parasitic infections. CLRs have many diverse functions depending on the signalling motifs in their cytoplasmic domains, and can induce endocytic, phagocytic, antimicrobial, pro-inflammatory or anti-inflammatory responses which are either protective or not during an infection. Understanding the role of CLRs in shaping anti-microbial immunity offers great potential for the future development of therapeutics for disease intervention. In this review we will focus on the recognition of bacterial, viral and parasitic pathogens by CLRs, and how these receptors influence the outcome of infection. We will also provide a brief update on the role of CLRs in antifungal immunity.