Although once a mainstay of drug discovery efforts within the pharmaceutical industry, enthusiasm for the use of natural products as a starting-point for the development of new medicines has steadily declined since the early 1990s. Today, the emerging field of synthetic biology is delivering the tools and technologies required to unlock the therapeutic potential of natural products. Lynden D. Room, Phillip W. Duke, James E. M. Stach and Paul R. Race illustrate how these approaches are circumventing many of the problems that have historically plagued conventional screening programmes, enabling the expedient discovery of new molecules with novel functions.