Deciphering the molecular basis of how modern human phenotypes have evolved is 
one of the most fascinating challenges in biology. Here, we will focus on the 
roles of gene regulatory factors (GRFs), in particular transcription factors 
(TFs) and long non-coding RNAs (lncRNAs) during human evolution. We will present 
examples of TFs and lncRNAs that have changed or show signs of positive 
selection in humans compared to chimpanzees, in modern humans compared to 
archaic humans, or within modern human populations. On the basis of current 
knowledge about the functions of these GRF genes, we speculate that they have 
been involved in speciation as well as in shaping phenotypes such as brain 
functions, skeletal morphology, and metabolic processes.