Laboratory testing is ubiquitous among hospitalized patients and is more common among patients in the intensive care unit (ICU). Despite its high cost and prevalence, there are few data to support the current practice of laboratory testing in most ICUs. Although testing offers considerable potential benefits, it is not without risk, including misleading results, iatrogenic anemia, and therapeutic actions of uncertain benefit. Laboratory testing should be conducted as part of a therapeutic approach to a clinical problem, mindful of pretest probability of disease, the performance of the selected test, and the relative benefits and risks of testing. Considering the indication for a particular test can lead to a more rational approach to laboratory testing and better use of available tests.