Most naturally occurring nucleotides and nucleosides areN-glycosyl derivatives of β-d-ribose. TheseN-ribosides are involved in most metabolic processes that occur in cells. They are essential components of nucleic acids, forming the basis for genetic information storage and flow. Moreover, these compounds are involved in numerous catalytic processes, including chemical energy production and storage, in which they serve as cofactors or coribozymes. From a chemical point of view, the overall structure of nucleotides and nucleosides is very similar and simple. However, their unique chemical and structural features render these compounds versatile building blocks that are crucial for life processes in all known organisms. Notably, the universal function of these compounds in encoding genetic information and cellular catalysis strongly suggests their essential role in the origins of life. In this review, we summarize major issues related to the role ofN-ribosides in biological systems, especially in the context of the origin of life and its further evolution, through the RNA-based World(s), toward the life we observe today. We also discuss possible reasons why life has arisen from derivatives of β-d-ribofuranose instead of compounds based on other sugar moieties.