Interindividual variation in gene expression has been convincingly shown to be controlled, in part, by genetic differences. Determining the architecture of genetic variation, the underlying gene expression may allow deeper insight into complex phenotypes, such as differences in disease susceptibility. Mapping genetic variants accounting for expression phenotypes in human cell and tissue panels has rapidly progressed from proof-of-principle experiments to general tools in biomedical discovery. We discuss the general approach and critical considerations for carrying out expression quantitative trait mapping in human tissues.