Dyspnoea and chest pain are common causes of referral to emergency departments. Both symptoms are non-specific and may be caused by ST elevation myocardial infarction, aortic dissection, pulmonary embolism, or infection. Fibrin D-dimer is often used for ruling out suspicion of acute diseases, but the clinical utility is limited by a modest specificity which lowers with age to approximately ten per cent at the age of 80 years. This review summarises the recommended approaches and highlights potential pitfalls when utilizing and interpreting fibrin D-dimer in the diagnostic work-up of commonly suspected medical conditions.