OBJECTIVES: To systematically assess the clinical and economic burden of invasive fungal infection (IFI) in Europe and to understand the value and treatment outcomes of diagnostic and empirical therapeutic approaches. METHODS: A comprehensive literature review was conducted using PubMed/MEDLINE and EMBASE (past 10 years) and relevant clinical societies (last 5 years) to identify epidemiology, outcomes, and treatment trends focusing on invasive Aspergillus and Candida infections using a defined protocol for inclusion/exclusion and data collection metrics. Clinical and economic burden outcomes described were incidence, mortality, overall healthcare resource utilization, length of hospital stay, and costs for IFI. RESULTS: Of 370 abstracts screened, 57 primary literature articles and 18 clinical society abstracts met inclusion criteria providing data from 12 European countries. No studies were identified in Eastern Europe and only two randomized, controlled studies comparing pre-emptive to empirical treatment were found. IFI incidence ranged from 3%-8% in empirical vs 8%-9% in pre-emptive treatment. Overall (IFI attributable) mortality ranged from 5%-41% (0%-24%) and 2%-17% (0%-13%) for non-comparative vs comparative studies, respectively. The highest mortality was found among critically ill patients, pediatric, and those with hematologic malignancies. The cost of IFI ranged from €8,351-€11,821 when evaluating hospitalizations and antifungals to €26,596-€49,216 when all direct costs for management were included. Costs for antifungal therapy alone were €3,930-€7,314. The incremental cost burden of IFI ranged from €10,530-€51,033 depending on the certainty of infection (possible, probable, proven) and duration of follow up.  CONCLUSIONS: IFI represents a substantial clinical and economic burden in critically ill and immunocompromised patients in Europe. IFI may account for up to 24% of mortality in these high risk populations and increase length of hospitalization by 20%. Differentiation of outcomes for pre-emptive and empirical treatment strategies have not been well defined and should be the focus of future clinical studies.