As the most abundant and renewable biopolymer, cellulose will continue to have an increasing role as a feedstock for engineered materials and biologically derived energy. Cellulose is the main structural fiber in plants and has already been used for millennia for heating, creating a diverse array of structures and tools, and for making paper. Although cellulose has been studied for over 150 years, with significant advances made over the past few decades on its biosynthetic pathway, structure and assembly, its synthesis and native structure remain a mystery. Given that the recalcitrance of cellulose, associated with its crystal-like structure, is a key obstacle in reducing cellulose into its monomeric glucose units useful for biofuel production, this lack of fundamental understanding of its structure and assembly is impacting the development of improved energy production technologies. In this article, the synthesis and structure of cellulose will be briefly reviewed along with key unanswered questions. Ideas are also presented which may shed light on observations of cellulose structure found in the literature and stimulate directions for future research.