The establishment of functional effects due to variation in concentrations of micronutrients in our diet is difficult since they are often not immediately recognized as being healthy or unhealthy. Indeed, effects induced by micronutrients are hard to identify and therefore the establishment of the recommended daily intake, the optimal intake and the upper limit pose a challenge. For bioactive food components this is even more complicated. Whole-genome transcriptome analysis is highly suitable to obtain unbiased information on potential affected biological processes on a whole-genome level. Here, we will describe and discuss several aspects of transcriptome analysis in benefit-risk assessment, including effect size, sensitivity and statistical power, that have to be taken into account to faithfully identify functional effects of micronutrients and bioactive food components.