In this chapter we describe recent developments in the practice of structure-based drug design (SBDD) and the computational methods that can be applied across a diversity of target classes. Recent technological advances are discussed that have enabled breakthroughs in membrane crystallography in particular in the field of G protein-coupled receptors. This review describes recent examples of SBDD applied to four specific target classes, kinases, proteases, protein–protein interactions and GPCRs. Overall, this is a large and rapidly moving field that is significantly impacting on drug development pipelines and the future success of the pharmaceutical industry. It is likely that a significant proportion of drugs in the future will be derived from structure- and fragment-based methods that can be used to complement other strategies in drug discovery.