ABSTRACT: With the widespread use of biomass for energy purposes, present communication exploits this potential renewable source for the production of bio-based products including chemicals, polymers, materials, feed and bioenergy, pursuing a cascading approach (biorefinery). Both biochemical (chemicals, enzymes, and fermentative microorganisms) and thermo-chemical (heat and chemical) processes, are addressed. It is true that substantial breakthrough has been achieved but the fact remains that R&D efforts are still necessary to address both technological and non-technological barriers. Development and demonstration of qualified innovative processes, technologies and components for the generation of both electric and thermal power in small-sized plants and the production of second-generation biofuels and sustainable biobased products, are the main challenges that needs to be addressed. In the above context, ENEA, in cooperation with both national and international stakeholders, has a number of R&D activities and a strategic projects portfolio. The focal point of ENEA’s activities as well as brief description of some prototype technologies, are described in the present communication.