STAR proteins regulate diverse cellular processes and control numerous developmental events. They function at the post-transcriptional level by regulating the stability, sub-cellular distribution, alternative splicing, or translational efficiency of specific mRNA targets. Significant effort has been expended to define the determinants of RNA recognition by STAR proteins, in hopes of identifying new mRNA targets that contribute their role in cellular metabolism and development. This work has lead to the extensive biochemical characterization ofthe nucleotide sequence specificity of a handful of STAR proteins. In contrast, little structural information is available to analyze the molecular basis of sequence specific RNA recognition by this protein family. This chapter reviews the relevant literature on STAR domain protein structure and provides insights into how these proteins discriminate between different RNA sequences.