Use of control (comparison) groups is a powerful research tool. In case-control studies, controls estimate the frequency of an exposure in the population under study. Controls can be taken from known or unknown study populations. A known group consists of a defined population observed over a period, such as passengers on a cruise ship. When the study group is known, a sample of the population can be used as controls. If no population roster exists, then techniques such as random-digit dialling can be used. Sometimes, however, the study group is unknown, for example, motor-vehicle crash victims brought to an emergency department, who may come from far away. In this situation, hospital controls, neighbourhood controls, and friend, associate, or relative controls can be used. In general, one well-selected control group is better than two or more. When the number of cases is small, the ratio of controls to cases can be raised to improve the ability to find important differences. Although no ideal control group exists, readers need to think carefully about how representative the controls are. Poor choice of controls can lead to both wrong results and possible medical harm.