The primary means of immobilizing enzymes are to boost the enzyme productivity and operational stability, alongside facilitating the reuse of enzymes. Notwithstanding the aforementioned benefits, enzyme immobilization promotes high catalytic activity and stability, convenient handling of enzymes, in addition to their facile separation from reaction mixtures without contaminating the products. This review describes the choices of support materials and cross-linkers together with several mechanisms that influence the performance, stabilization and hyperactivation of immobilized enzymes. Altering enzyme properties often changes the enzyme structure due to random modifications in the behavior, which in some cases can be positive or negative. Future strategy to develop new generations of immobilized enzymes should capitalize on the rapid advances of genetic manipulation, organic chemistry, computational chemistry and bioinformatics, reactor and reaction design. Upcoming efforts to improve enzymes as industrial biocatalysts must consider their development for increased selective promiscuity suitable for multiple biotransformations, either independently or as catalytic cascade processes thereby enhance the cost-effectiveness of the processes.