Rye is one of the most important crops in Eastern and Northern Europe. Despite the numerous beneficial features of rye, its annual production decreases successively which correlates with the lack of progress in its breeding compared with other cereals. Biotechnological methods could effectively improve the breeding of rye. However, their application is highly limited by the absence of an efficient procedure for plant regeneration in vitro, since rye is one of the most recalcitrant cereals with regard to the tissue culture response (TCR), and successful regeneration is highly dependent on genotype. Efforts to understand the genetic mechanisms controlling TCR of rye have elucidated some basic aspects, and several genes and genome regions controlling this trait have been identified. The aim of this review is to summarize the limited current knowledge of this topic.