Abstract Biofloc technology is instrumental in improving growth performance and yield in shellfish aquaculture, while leading to enhanced water quality through maintaining the nutrients level within a safe range. More specifically, toxic nitrogenous wastes are converted into beneficial microbial biomass known as “biofloc”, contributing to improve shellfish immune system. Among the various parameters affecting the efficiency of the process is the carbon source and C:N ratio. In light of these, the present work critically reviews the effects of biofloc systems on growth performance, immunity and diseases resistance in shellfish production. Moreover, it scrutinizes the microbial diversity and nutritional composition of biofloc. Then, the application of the technology in various shellfish cultures, including shrimp, freshwater prawn, crabs, crayfish, clam, and oyster, is presented. Overall, biofloc systems contribute to enhanced shellfish survival rate to the highest value of 96–100% for marine shrimp, 95–99% for freshwater prawn, 70–83% for crayfish, 83–100% for oyster, Crassostrea sp. and up to 2% for mud crabs larvae through substantially reducing the ammonia level in the culture (summarized in Table 1 – Table 5). Finally, the main challenges in utilizing biofloc systems, i.e., suitable aeration and mixing and microbial mechanisms involved are also explained to shed light on future research directions in the field.