Although considered to be a rare infection, mucormycosis (zygomycosis) has emerged as the second most common invasive mould infection. Despite the advent of newer antifungal agents, mortality rate of mucormycosis remains exceedingly high. Successful management of mucormycosis requires early diagnosis, reversal of underlying predisposing risk factors, surgical debridement and prompt administration of active antifungal agents. However, mucormycosis is not always amenable to cure. There are challenging obstacles that lead to difficulties in management of amphotericin B. These include unique host-based risk factors for mucormycosis, the fungus' resistance to innate host defences and distinctive features of its immunopathogenesis, such as extensive angioinvasion, increased virulence and use of chelators by the fungus as siderophores. In addition to these obstacles, the difficulties in early diagnosis, including nonspecific clinical manifestations, lack of serological methods, as well limitations of culture and molecular methods, lead to delay in initiation of antifungal therapy. Finally, the variability of susceptibility to amphotericin B and resistance to most other conventional antifungal agents leads to major limitations in successful treatment of this devastating infection.