In functional magnetic resonance imaging (fMRI), hemispheric dominance is generally indicated by a measure called the laterality index (LI). The assessment of a meaningful LI measure depends on several methodological factors that should be taken into account when interpreting LI values or comparing between subjects. Principally, these include the nature of the quantification of left and right hemispheres contributions, localisation of volumes of interest within each hemisphere, dependency on statistical threshold, thresholding LI values, choice of activation and baseline conditions and reproducibility of LI values. This review discusses such methodological factors and the different approaches that have been suggested to deal with them. Although these factors are common to a range of fMRI domains, they are discussed here in the context of fMRI of the language system.