Since its inception almost 15 years ago, synthetic biology has evolved into a vibrant and productive field, owing in large part to the use of model microorganisms for the design, creation and implementation of both simple and more sophisticated biological systems. This Focus issue of Nature Reviews Microbiologypresents a set of specially commissioned articles that together chart the technological and cultural developments of the field, provide a framework for the use of emerging synthetic devices for microbial engineering, discuss the use of alternative microorganisms for industrial-scale applications and describe the first successful 'real-world' application that has been achieved. The Focus issue is accompanied by a joint Web Special withNature MethodsandNature.