Over the past few years, there has been a growing realization that metabolic pathways must be studied in the context of the whole cell rather than at the single pathway level, and that even the simplest modifications can send ripples throughout the entire system. Attention has therefore shifted away from reductionist, single-gene engineering strategies and towards more complex approaches involving the simultaneous overexpression and/or suppression of multiple genes. The use of regulatory factors to control the abundance or activity of several enzymes is also becoming more widespread. In combination with emerging methods to model metabolic pathways, this should facilitate the enhanced production of natural products and the synthesis of novel materials in a predictable and useful manner.