Advanced biorefineries, which aim at valorizing biomass (from agriculture, forestry, aquaculture, among others) into a wide spectrum of products and bioenergy, are seen today as key to implement a sustainable biobased economy. Although different concepts of biorefinery are currently under development, further research and improvement are still required to obtain environmentally friendly and economically feasible commercial scale biorefineries. Valorization of all biomass components and integration of different disciplines are some of the strategies that have been considered to improve the economic and environmental performance. This paper summarizes and discusses the most recent innovations and strategic orientations for the development of advanced biorefineries. Focus is given on the valorization of non-carbohydrate components of biomass (protein, acetic acid and lignin), on-site and tailor-made production of enzymes, big data analytics, and interdisciplinary efforts. The idea is to provide new insights and directions to support the development and large-scale implementation of biorefineries.