Invasive fungal infections are associated with high morbidity and mortality in critically ill patients due, in part, to diagnostic difficulties in the early stages. Nonculture-based techniques such as (1,3)-β-d-glucan, galactomannan, mannan and antimannan antibodies, Candida albicans germ tube-specific antibodies or fungal DNA are required for earlier diagnosis, prognostic information and monitoring outcome. A decision-tree algorithm based on the combination of nonculture-based techniques is suggested to optimize the diagnosis and evolution of critically ill patients at risk of invasive mycoses. The use of (1,3)-β-d-glucan and blood cultures twice a week is proposed; if positive, treatment initiation is recommended alongside the performance of the nonculture-based microbiological tool depending on suspected mycoses and the availability of techniques.