Given the high mortality of invasive infections caused by filamentous fungi and the limitations of current antifungal therapies, the interest in combination therapy is increasing. However, assessment of the nature and the intensity of antifungal interactions depends on the in vitro methodology used as well as on the approach chosen to analyse the data. Regarding in vitro methodology, despite the considerable progress that has been made with the M-38P standard proposed by the National Committee Clinical Laboratory Standards (NCCLS), many variables in antifungal susceptibility testing of filamentous fungi such as the inoculum, incubation conditions, medium and minimal inhibitory concentration (MIC) endpoints remain unstandardized. Visual determination of the MIC is subjective and does not allow precise quantification of fungal growth, thus hindering the modelling of the concentration-dependent effects of antifungal drugs on filamentous fungi. Colorimetric assays based on the conversion of tetrazolium salts may help to overcome these problems and enable the development of modern approaches to modelling the interaction of antifungal drugs with moulds. Regarding the modelling of drug interactions, various models have been developed based on non-parametric and parametric approaches of the two main competitors - the Loewe additivity and the Bliss independence - to the zero interaction theory. The standard approach in medical microbiology has been the calculation of a fractional inhibitory concentration index but this appears not to be suitable for moulds. Alternative approaches of drug interaction modelling consist of response surface approaches and fully parametric models which incorporate modern concepts of statistical and regression analysis and provide an objective and quantitative tool for the study of drug interaction.