Effective techniques for conducting high-pressure and high-temperature single-crystal X-ray diffraction experiments were developed in the 1970s. By the end of that decade a number of papers had been published that defined optimal methods for operating diffractometers, especially for high-pressure experiments. The following decade saw the spread of the techniques from the institutions involved in the original developments into many other, mostly mineralogical, crystallography laboratories around the world. The state of the art of high-pressure diffractometry as it stood in the early 1980s was summarized in Comparative Crystal Chemistry (Hazen and Finger 1982). Since that time, advances in computing capacity and in the mechanical quality of diffractometers have been combined to increase the precision of high-pressure measurements by an order of magnitude. This chapter, while building on the work summarized in Hazen and Finger (1982), extends it on the basis of the experience gained by the authors and others in the intervening years. The aim of this chapter is to provide a crystallographer with no previous experience in high-pressure or high-temperature crystallography with the information to set up, or to convert, a diffractometer for such work as well as a detailed guide as to how such experiments should be carried out. We hope thereby to answer the questions “How do I modify my diffractometer for high-P,T experiments?” in the next section, and “How do I do the experiment?” in the following one. The last section of this chapter describes the modifications to data reduction procedures that must be made for handling data collected from crystals in diamond-anvil cells (DAC). Issues relating to DAC design and furnace design are addressed in Miletich et al. (this volume) and Yang and Peterson (this volume) respectively. Some basic familiarity with the operation of single-crystal diffractometers for conventional measurements at room conditions is assumed, although …