Non-neoformans cryptococci have been generally regarded as saprophytes and rarely reported as human pathogens. However, the incidence of infection due to these organisms has increased over the past 40 years, with Cryptococcus laurentii and Cryptococcus albidus, together, responsible for 80% of reported cases. Conditions associated with impaired cell-mediated immunity are important risks for non-neoformans cryptococcal infections and prior azole prophylaxis has been associated with antifungal resistance. The presence of invasive devices was a significant risk factor for Cryptococcus laurentii infection (adjusted OR = 8.7; 95% CI = 1.48-82.9; p = 0.003), while predictors for mortality included age > or =45 years (aOR = 8.4; 95% CI = 1.18-78.82; p = 0.004) and meningeal presentation (aOR = 7.0; 95% CI = 1.85-60.5; p= 0.04). Because clinical manifestations of non-neoformans cryptococcal infections are most often indistinguishable from Cryptococcus neoformans, a high index of suspicion remains important to facilitate early diagnosis and prompt treatment for such infections.