Many studies have been conducted on the co-firing of coal and biomass for carbon reduction. However, only some have examined using 100% biomass as the primary fuel in large-scale circulating fluidized bed (CFB) boilers. This review examines the feasibility and challenges of transitioning large-scale CFB boilers from coal-biomass co-firing to utilizing 100% palm kernel shells (PKS) and woodchips. CFB technology offers inherent advantages for biomass combustion, including fuel flexibility and lower operating temperatures, but several technical barriers must be overcome to ensure efficient and reliable operation. The review analyzes key challenges, including managing high ash content, mitigating emissions, agglomeration, fouling, slagging, corrosion, optimizing combustion efficiency, and ensuring long-term operational reliability. The review examines potential solutions, such as fuel pre-treatment techniques, biomass co-firing, combustion optimization control, advanced ash management systems, heat recovery, and the application of computational modeling tools like Computational Particle Fluid Dynamics (CPFD) to simulate and optimize boiler design and operation. Though challenges remain, transitioning large-scale CFB boilers to 100% PKS and woodchip firing presents a significant opportunity to advance sustainable energy production. Further research and development of innovative solutions tailored to the unique properties of PKS and woodchips are crucial to unlocking the full potential of these biomass resources.