Biocatalysis is becoming a transformational technology for chemical synthesis as a result of recent advances in large-scale DNA sequencing, structural biology, protein expression, high throughput screening, and enzyme evolution technologies. To truly impact chemical synthesis at the industrial scale, enzyme discovery, biocatalyst optimization, process design, and development must be integrated in order to deliver cost-effective and green chemistry solutions for drug manufacture. In this article, some recent applications of biocatalysis in developing chemoenzymatic processes were selected to illustrate the principle of this integrated approach. The emphasis will be directed to those examples where the chemoenzymatic route represents a second-generation process developed to replace the existing chemical one.