In the last years, the incidence of the invasive infection by moulds has increased. Also, the characteristics of invasive mycosis are changing due to the description of new pathogenic species and also because strains and species resistant to antifungal drugs are appearing. The development of mould antifungal drug resistance is the inevitable and logical consequence of their clinical use, although the frequency and clinical relevance of this is unknown. In this text current mould antifungal drugs resistance mechanisms are reviewed. The study of molecular mechanisms of antifungal drug resistance is the most valuable strategy to resistance development control and also in helping to develop safer and more active molecules able to avoid them. In the meanwhile is important the correct use of the available tools: epidemiological surveillance of resistance emergence and to use all the efforts towards prompt diagnosis in order to accomplish an adequate and effective treatment.