Dectin-1 is a C-type lectin receptor (CLR) expressed on the surface of various mammalian myeloid cells. Dectin-1 recognizes β-glucans and elicits antifungal proinflammatory immune responses. Recent studies have begun to examine the biology of Dectin-1 in previously less explored settings, such as homeostasis, sterile inflammation, and in the central nervous system. Indeed, in certain contexts, Dectin-1 is now known to promote tolerance, and anti-inflammatory and neuroprotective responses. In this review, we provide an overview of the current understanding of the roles of Dectin-1 in immunology beyond the context of fungal infections, mainly focusing on in vivo neuroimmunology studies, which could reveal new therapeutic approaches to modify innate immune responses in neurologic disorders.