Biocatalytic synthesis of enantiomerically pure compounds for pharmaceutical intermediates is gaining momentum. This is the result of advances in genomics, screening and evolution technologies leading to the increased availability of new and robust biocatalysts suited for industrial-scale application, and is stimulated by an increased demand for catalysts that are able to address the increased complexity of active pharmaceutical ingredients. The vast majority of biotransformation reactions for the manufacturing of optically active pharmaceutical intermediates are still based on enantioselective ketone reductions and enantiospecific hydrolyses. This review aims to point at alternative reaction types and integrated multi-enzymatic steps that are emerging in large-scale applications.