Even though the search for alternative fuels from lignocellulosic biomass started a few decades ago, still it is relatively immature mainly because of few challenges which are yet to be solved for making the process commercially viable. The main challenge is the higher production cost of lignocellulose degrading enzymes. There are many factors need to be considered on lignocellulosic biomass degrading enzymes for practical applications mainly due to the heterogeneity of the biomass. A single enzyme will not degrade the biomass efficiently hence it needs to consider for a cocktail of enzymes. Similarly, one enzyme cocktail will not work on every biomass types due to the compositional variability. All these factors need to be addressed which makes the research tiresome. Also, there are several gaps in enzyme technology, especially for biofuel applications. The present review addresses the lacuna in research on lignocellulose degrading enzymes for biofuel production and possible solutions.