<abstract> <p>Cryptococcal meningitis (CM) is a dominant cause of morbidity and mortality among patients with human immunodeficiency virus/ acquired immune deficiency syndrome (HIV/AIDS) caused by <italic>Cryptococcus neoformans</italic> and <italic>Cryptococcus gattii</italic> species complex. The complex is composed of closely related members, yet with diverse epidemiology, pathogenesis, and drug-resistant pattern. Cell-mediated immunity is the strongest pillar in immunity to cryptococcosis, further worsening HIV/AIDS patients' scenario. Antifungal resistance and immune evasion again tilt the host-parasite balance in favor of the fungal pathogen. In this regard, researchers are actively challenged to discover immunotherapy and vaccine for CM, to produce specific treatment and prevention that will address CM conventional therapeutics failure. As the major capsular polysaccharide of the <italic>Cryptococcus</italic>, which is tightly linked to pathogenicity, immunogenicity, and immune evasion, the glucuronoxylomannan (GXM) is cardinally targeted for vaccine and immunotherapy development. Further, the amount of GXM shed in body fluids correlates with the disease severity. Herein, we reviewed the literature with the journey so far in line with GXM as the salient immunological target on cryptococcosis.</p> </abstract>