Cluster headache (CH), a primary neurovascular headache syndrome, is characterized by recurrent, unilateral, short-lasting attacks of excruciating pain in the temporal and/or orbital region. The pain is considered one of the most severe pain conditions known to humans. Compared with the general population, first-degree relatives of probands with CH have a significantly increased risk of the same disorder. However, there seems to be no clear mode of inheritance, suggesting that both genetic and environmental factors are of importance, with the pathophysiology being multifactorial. Despite the genetic influence of the disease, a low prevalence and small pedigrees complicate the feasibility of genetic studies. To date, only genetic studies with limited sample sizes have been performed, but results have indicated an association with the HCRTR2 gene, which is involved in the regulation of chronobiological rhythms. Collaborative multicenter studies on large clinically well-defined materials are needed to reach a better understanding of the complex genetic background of CH.