Direct cellulose fermentation by cellulolytic anaerobic bacteria offers potential to generate renewable hydrogen (H(2)) from inexpensive "waste" cellulosic feedstocks. The rates and yields of H(2) production via direct cellulose fermentation are low and must be increased significantly if this technology is to become a viable method for generating usable H(2). A much more comprehensive understanding of the relationships between gene and gene product expression, end-product synthesis patterns, and the factors that regulate carbon and electron balance, within the context of the bioreactor conditions must be achieved if we are to improve molar yields of H(2) during cellulose fermentation. Strategies to increase yields of H(2) production from cellulose include manipulation of carbon and electron flow via end-product inhibition (metabolic shift), metabolic engineering at the genetic level, synergistic co-cultures, and bioprocess engineering and bioreactor designs that maintain a neutral pH during fermentation and ensure rapid removal of H(2) and CO(2) from the aqueous phase. (C) 2009 International Association for Hydrogen Energy. Published by Elsevier Ltd. All rights reserved.