Mannose receptor (MR) is a C-type lectin primarily expressed by macrophages and dendritic cells. Its three distinct extracellular binding sites recognise a wide range of both endogenous and exogenous ligands, therefore MR has been implicated in both homeostatic processes and pathogen recognition. However, the function of MR in host defence is not yet clearly understood as MR-deficient animals do not display enhanced susceptibility to pathogens bearing MR ligands. This scenario is even more complex when considering the role of MR in innate immune activation as, even though no intracellular signalling motif has been identified at its cytoplasmic tail, MR has been shown to be essential for cytokine production, both pro-inflammatory and anti-inflammatory. Furthermore, MR might interact with other canonical pattern recognition receptors in order to mediate intracellular signalling. In this review, we have summarised recent observations relating to MR function in immune responses and focused on its participation in phagocytosis, antigen processing and presentation, cell migration and intracellular signalling.