Creutzfeldt-Jakob disease (CJD) is a prion disease characterized by rapid neurodegeneration that leads to the death of the patient within months to a few years. Since the disease is transmissible, there is an obligation in Sweden to report possible CJD cases to the Swedish Institute for Infectious Disease Control. To make a diagnosis of CJD is difficult, especially early in the course of the disease when the clinical features may be very vague and heterogeneous. Hence, accurate biological markers both for confirming and excluding CJD would be of great value. The currently recommended investigation of a patient with possible CJD comprises clinical evaluation. electroencephalography, computed tomography or magnetic resonance imaging of the brain and test for 14-3-3 protein in the cerebrospinal fluid (CSF). Recent studies suggest that analysis of total tau (T-tau) and phospho-tau (P-tau) in CSF is a valuable complement to this set of investigations. Here, we review how CSF T-tau and P-tau may aid in the diagnosis of CJD and illustrate this by presenting cases from routine clinical practice.