The identification of hypothermia as the cause of death has always been somewhat problematic in forensic pathology because of unspecific, inconstant, or even negative macroscopic and microscopic findings. Though the simultaneous presence of frost erythema, Wischnewski spots, hemorrhages into the synovial membrane, bloody discoloration of synovial fluid of the knee, and basal vacuolization of the renal tubular epithelial cells has been indicated as strongly supportive of fatal hypothermia, their absence does not allow the diagnosis of hypothermia to be ruled out. Postmortem biochemical investigations are valuable in detecting adaptation responses to cold stress and metabolic changes that occur following cold exposure. However, ethanol intoxication prevents appearance of adaptation responses to cold, rendering the diagnosis less obvious. Immunohistochemistry, postmortem imaging, and molecular pathology have shown promising results, although at present, they do not provide pathognomonic signs of fatal hypothermia. The aim of this article is to present a review of the literature covering the significance of different postmortem investigations that are associated with hypothermia fatalities.