• Changes in gene expression likely account for most phenotypic divergence between modern and archaic humans. • Archaic gene expression cannot be readily measured from ancient remains because of the rapid degradation of RNA. • Alternative approaches use introgression, genome engineering, and statistical prediction to infer expression divergence. • Introgressed regulatory sequences have contributed to variation in modern human gene expression, phenotypes, and fitness. Differences in gene expression are thought to account for most phenotypic differences within and between species. Consequently, gene expression is a powerful lens through which to study divergence between modern humans and our closest evolutionary relatives, the Neanderthals and Denisovans. Such insights complement biological knowledge gleaned from the fossil record, while also revealing general features of the mode and tempo of regulatory evolution. Because of the degradation of ancient RNA, gene expression profiles of archaic hominins must be studied by indirect means. As such, conclusions drawn from these studies are often laden with assumptions about the genetic architecture of gene expression, the complexity of which is increasingly apparent. Despite these challenges, rapid technical and conceptual advances in the fields of ancient genomics, functional genomics, statistical genomics, and genome engineering are revolutionizing understanding of hominin gene expression evolution. [ABSTRACT FROM AUTHOR]