Cold shock domain (CSD)‐containing proteins have been found in all three domains of life and function in a variety of processes that are related, for the most part, to post‐transcriptional gene regulation. The CSD is an ancient β‐barrel fold that serves to bind nucleic acids. The CSD is structurally and functionally similar to the S1 domain, a fold with otherwise unrelated primary sequence. The flexibility of the CSD/S1 domain for RNA recognition confers an enormous functional versatility to the proteins that contain them. This review summarizes the current knowledge on eukaryotic CSD/S1 domain‐containing proteins with a special emphasis on UNR (upstream of N‐ras), a member of this family with multiple copies of the CSD.