Changes in genetic regulation contribute to adaptations in natural populations and influence susceptibility to human diseases. Despite their potential phenotypic importance, the selective pressures acting on regulatory processes in general and gene expression levels in particular are largely unknown. Studies in model organisms suggest that the expression levels of most genes evolve under stabilizing selection, although a few are consistent with adaptive evolution. However, it has been proposed that gene expression levels in primates evolve largely in the absence of selective constraints. In this article, we discuss the microarray-based observations that led to these disparate interpretations. We conclude that in both primates and model organisms, stabilizing selection is likely to be the dominant mode of gene expression evolution. An important implication is that mutations affecting gene expression will often be deleterious and might underlie many human diseases.