D-dimers, as a product of cross-linked fibrin clot degradation, are one of the most frequently measured laboratory parameters. Their formation requires the activation of both the coagulation cascade and the fibrinolysis system, providing valuable information about the body’s coagulation state. Changes in D-dimers levels are observed in both pathological and physiological conditions. There are several methods used to evaluate D-dimers level but most of them rely on reactions with monoclonal antibodies. In the diagnosis of venous thromboembolism (VTE), D-dimers level below 500 μg/L can, with high probability, rule out the disease in asymptomatic patients. D-dimers reach heightened levels in disseminated intravascular coagulation syndrome (DIC) and are a component of diagnostic scales. Their level within the normal range excludes the presence of this syndrome. The increase in D-dimers levels in the course of cancer is associated with the degree of progression, type and prognosis of cancer. The causes of the increase in D-dimers concentration can also be found in the course of a thromboembolic event associated with SARS-CoV-2 infection. Situations in which D-dimers can be elevated also include pregnancy, childbirth, inflammatory diseases or age-related changes.