BACKGROUND d-dimer is a reliable and sensitive index of fibrin deposition and stabilization. As such, its presence in plasma should be indicative of thrombus formation. There are many conditions unrelated to thrombosis in which d-dimer concentrations are high, however, making its positive predictive value rather poor. CONTENT Notwithstanding these limitations, d-dimer can be regarded as a most valuable laboratory tool to diagnose and manage a vast array of thrombosis-related clinical conditions, including (a) diagnosis of venous thromboembolism (VTE), (b) identification of individuals at increased risk of first thrombotic event (both arterial and venous), (c) identification of individuals at increased risk of recurrent VTE, (d) establishment of the optimal duration of secondary prophylaxis after a first episode of VTE, (e) pregnancy monitoring, and (f) diagnosis/monitoring of disseminated intravascular coagulation (DIC). This article is aimed at reviewing the merits and pitfalls of these applications. SUMMARY From my analysis of the literature, I draw the following conclusions. (a) d-dimer, as measured by a sensitive test, can be safely used to exclude VTE in symptomatic outpatients, provided that it is used in combination with the pretest clinical probability. (b) High concentrations of d-dimer are associated with an increased risk of recurrent VTE. (c) Patients who present with d-dimer above cutoff after stopping the regular course of oral anticoagulation benefit from extended prophylaxis. (d) Finally, d-dimer can be used as a fibrin-related degradation marker for the diagnosis/management of patients with DIC.