Laboratory monitoring is widely recommended to measure the anticoagulant effect of unfractionated heparin and to adjust the dose to maintain levels in the target therapeutic range. The most widely used laboratory assay for monitoring unfractionated heparin therapy is the activated partial thromboplastin time (aPTT). A fixed therapeutic range for the aPTT of 1.5 to 2.5 times the control value has become widely accepted, but the evidence supporting this range is weak and the clinical validity of using the aPTT for predicting thrombotic or bleeding events is questionable. The aPTT test is also affected by numerous preanalytic and analytic variables that are unrelated to the anticoagulant effect of unfractionated heparin, further eroding its potential value for monitoring unfractionated heparin treatment. Unfractionated heparin dose appears to be more important than the aPTT in predicting clinical efficacy. Despite serious limitations, the reliance on the aPTT is likely to continue because of its ready availability and familiarity of clinicians with the test. The focus of clinicians who manage unfractionated heparin therapy should be to ensure that an adequate starting dose of unfractionated heparin is used and that the aPTT method is standardized. Future research efforts should be directed towards developing methods to improve standardization of the aPTT assay for monitoring unfractionated heparin. Direct measures of the concentration of unfractionated heparin in the blood are attractive because these assays are not affected by many of the biologic variables that interfere with the aPTT and may be suitable for automation. However, currently available unfractionated heparin assays are much more expensive than the aPTT, are not widely available, and their validity has not been adequately assessed in clinical outcome studies.