Characteristics that would make enzymes more desirable for industrial applications can by improved using Directed Evolution. This process allows evolution of enzymes in the laboratory via iterative cycles of mutagenesis and screening for superior properties. We developed a directed evolution technique called Random Drift Mutagenesis (RNDM). Mutant populations are screened and all functional mutants are collected and put forward into the next round of mutagenesis and screening. The goal of this technique is to evolve enzymes by rapidly accumulating mutations and exploring a greater sequence space by providing minimal selection pressure and high throughput screening. Our target enzyme is a beta-glucosidase isolated from the thermophilic bacterium, Caldicellulosiruptor saccarolyticus that is not end-product inhibited and cleaves cellobiosde resulting from endoglucanase hydrolysis. Our screening method is Fluorescence Activated Cell Sorting (FACS). FACS is an attractive method for assaying mutant enzyme libraries because individual cells can be screened, sorted into distinct populations and collected very rapidly. It is possible to screen 10,000 mutants per second using the FACSAriaTM system. However, FACS screening poses several challenges, in particular, maintaining the link between genotype and phenotype because most enzyme substrates do not remain associated with the cells. We employed a technique called In Vivo compartmentalization (IVC) where whole cells can be encapsulated in cell-like structures along with the enzyme substrate. We present how we have used RNDM, in combination with IVC, to create and screen mutant beta-glucosidase libraries which then can be further improved by a gene shuffling technique such as Degenerate Oligonucelotide Gene Shuffling.