Global energy demand is primarily dependent on the fossil fuel resources and the energy consumption is growing significantly that will cause increased concentration of greenhouse gases (GHG) in the atmosphere and depletion of known non-renewable energy resources that will cause threat to future energy security. The fossil resources are regarded as un-sustainable in terms of economy, ecology and environmental perspective. The increased utilization of biomass can play a significant role in replacing conventional fossil-based fuels and reducing emissions due to strict regulations for reducing greenhouse gas (GHG) emissions. Biomass based fuels can contribute as additional energy resource in the global energy mix. This chapter has discussed first generation biofuel, concept of bio-refineries, first generation feedstock derived bio-fuels, global first generation biofuel producing countries/regions and major sustainability challenges. The most common first generation biofuels include bio-ethanol, bio-diesel and bio-gas derived mainly from corn, sugarcane, soybean, vegetable oil, palm oil, wastes etc. From the sustainability perspective, first generation biofuels face numerous sustainability challenges including food and fuel competition, change in land-use, potential increased GHG emissions due to fossil fuel utilization in the upstream processes. First generation biofuels appears unsustainable because of the potential stress that their production places on food commodities. The economic aspects of first generation biofuel largely depend upon the type of feedstock and region where the feedstock have been cultivated and produced. Food prices will be affected due to increased production of energy crops that potentially compete with food crops for land use. In addition, the substantial production of biomass and conversion of biomass feedstock to biofuel may create new jobs and increase revenue from the agricultural sector.