Directed evolution is becoming a widely used technique for modifying or enhancing enzyme performance. Ultimately, the success of directed protein evolution experiments hinges on the efficiency of the methods used to screen libraries for mutants with properties of interest. Recent advances in library design, and methods of random mutagenesis, combined with new screening and selection tools, continue to push forward the potential of directed evolution. The power of cell surface-display techniques for the selection of novel enzymes is greatly improving the library size and hence the sequence space that can be searched.