: Crimean-Congo hemorrhagic fever (CCHF) is a potentially severe tick-borne viral disease endemic in several regions of Europe, Africa, and Asia. Rapid and reliable diagnosis is essential for early initiation of patient's treatment and for prompt implementation of appropriate precaution and infection control measures to prevent further spread of the disease. : A literature search was undertaken on available approaches for laboratory diagnosis of CCHF infections, and the advantages and limitations of the assays are discussed. : Given that the genetic variability among CCHFV strains is high, attention has to be paid on the molecular protocols to detect all currently known genetic lineages of the virus as the emergence of CCHFV strains belonging to various lineages in new environments is not unexpected. In severe cases, the antibody production may be delayed or absent. It is important that the laboratories involved in CCHFV diagnostics to run quality control assays. Standardized assays and point-of-care tests with high sensitivity and specificity are needed. It is expected that the application of next-generation sequencing will be a powerful tool for CCHF diagnostics. Awareness, preparedness, and surveillance are required for prompt detection of CCHF cases.