Gene expression can be studied at a genome-wide scale with the aid of modern microarray technologies. Expression profiling of tens to hundreds of individuals in a genetic population can reveal the consequences of genetic variation. In this paper it is argued that the design and analysis of such a study is not a matter of simply applying the existing and more-or-less standard computational tools for microarrays to a new type of experimental data. It is shown how to fully exploit the power of genetics through optimal experimental design and analysis for two major microarray technologies, cDNA two-colour arrays and Affymetrix short oligonucleotide arrays.