The article discusses the classification and functional diversity of SF1 and SF2 helicases, which are enzymes involved in various aspects of RNA and DNA metabolism. Despite sharing a highly conserved catalytic core, different SF1 and SF2 helicases perform a wide range of functions on diverse substrates. The authors propose a classification based on protein families characterized by typical sequence, structural, and mechanistic features. This classification highlights major structural and functional themes for these proteins and complements existing categorizations. The article also reviews recent data on the structure and function of SF1 and SF2 helicases, emphasizing the importance of understanding the communication between nucleic acid and ATP binding sites, as well as the role of terminal accessory domains in defining the function of helicases. The authors conclude by discussing the challenges and future directions in the study of SF1 and SF2 helicases, including the need for more comprehensive structural and mechanistic studies.The article discusses the classification and functional diversity of SF1 and SF2 helicases, which are enzymes involved in various aspects of RNA and DNA metabolism. Despite sharing a highly conserved catalytic core, different SF1 and SF2 helicases perform a wide range of functions on diverse substrates. The authors propose a classification based on protein families characterized by typical sequence, structural, and mechanistic features. This classification highlights major structural and functional themes for these proteins and complements existing categorizations. The article also reviews recent data on the structure and function of SF1 and SF2 helicases, emphasizing the importance of understanding the communication between nucleic acid and ATP binding sites, as well as the role of terminal accessory domains in defining the function of helicases. The authors conclude by discussing the challenges and future directions in the study of SF1 and SF2 helicases, including the need for more comprehensive structural and mechanistic studies.