Production of butanol is adversely affected by the high costs of traditional substrates such as glucose, corn, sugarcane molasses, and whey permeate. To reduce the cost of production, this biofuel could be produced from economically available renewable feedstocks such as corn stover, wheat, barley, and rice straws, corn fiber, switchgrass, alfalfa, reed canary grass, sugarcane bagasse, miscanthus, waste paper, distillers dry grains and solubles (DDGS), and soy molasses. Currently, costs of corn stover, grasses, and straws are in the range of $24-60/ton as opposed to corn which has ranged from $153-218/ton during recent months. It should be noted that while prices of these residue feedstocks are low, they are associated with additional process steps such as pretreatment, and hydrolysis prior to fermentation. Additionally, fermentation inhibitors are generated during the pretreatment process which either halt or slow down reaction rates or fermentation. This section describes production of butanol from wheat straw, barley straw, corn stover, switchgrass, corn fiber, and DDGS and challenges that are faced when handling these feedstocks for the production of this biofuel.