The control of gene expression is a biological process essential to all organisms. This is accomplished through the interaction of regulatory proteins with specific DNA motifs in the control regions of the genes that they regulate. Upon binding to DNA, and through specific protein protein interactions, these regulatory proteins convey signals to the basal transcriptional machinery, containing the respective RNA polymerases, resulting in particular rates of gene expression. In eukaryotes, in addition and complementary to the binding of regulatory proteins to DNA, chromatin structure plays a role in modulating gene expression. Small RNAs are emerging as key components in this process. This chapter provides an introduction to some of the basic players participating in these processes, the transcription factors and co-regulators, the cis-regulatory elements that often function as transcription factor docking sites, and the emerging role of small RNAs in the regulation of gene expression.