The fungal genusCryptococcuscomprises a group of pathogens with considerable phenotypic and genotypic diversity that can lead to cryptococcosis in both healthy and immunocompromised individuals. With the emergence of the HIV pandemic, cryptococcosis, mainly meningoencephalitis, afflicts HIV-infected patients with severe dysfunction of T cells. It has also been reported in recipients of solid organ transplantation and in patients with autoimmune diseases who take immunosuppressive agents long-term, as well as in those with unidentified immunodeficiency. The clinical outcome of the disease is primarily determined by the immune response resulting from the interplay between the host immune system and the pathogen. Most human infections are caused byCryptococcus neoformans, and nearly all immunological studies have focused onC. neoformans. This review provides an updated understanding of the role of adaptive immunity during infection withC. neoformansin human and animal models over the past half-decade.