This chapter is designed to provide a comprehensive, systematic account of the methods of conducting clinical research in resuscitation, in particular, how to set up and carry out a comprehensive and meaningful clinical trial. We will follow the natural conduct of a study, from designing the protocol through data collection to evaluation and interpretation. As an example of some of the difficulties and also the satisfactions of a job well done, in the Appendix we present Professor Wenzel's personal description of the trials and tribulations of determining the role of vasopressin in treatment for cardiac arrest.