The use of 'design of experiments' (DoE) is a revolutionary approach to optimisation and screening of experimental parameters. Simple experimental designs and statistical tools for data analysis can provide much information about the system under investigation after only a few experiments. Such information can be key in decision-making for further experiments and can enable the development of robust and reliable protocols for chemical synthesis, analytical methods or biological assays. Coupling of design of experiments with modern high-throughput automation systems has the potential to maximise the capabilities of these systems and give increased productivity for many drug discovery applications.