Recent progress in the characterization of two groups of genes responsible for natural differences in frost tolerance in wheat and barley is reviewed here. The first group includes the vernalization genes that delay flowering until the end of the winter and protect sensitive floral primordia. This process is regulated mainly by differences in the regulatory regions of VRN1 and VRN3 genes or in the coding regions of VRN2. The second group includes a set of tandemly duplicated CBF (C-repeat Binding Factors) transcription factors at the FR2 (Frost Resistance 2) locus. CBF transcription factors are known regulators of the COR genes (COld Regulated genes) which are induced by cold and confer tolerance to subsequent freezing temperatures (acclimation). Natural differences in frost tolerance in both wheat and barley have been mapped to the FR2 locus, and are associated with differences in threshold induction temperatures and/or transcript levels of several CBF genes. Higher threshold induction temperatures result in earlier up-regulation of COR genes during the fall, whereas higher induction levels by cold are associated with faster cold acclimation rates. Both processes result in longer acclimation periods and improved frost tolerance. Increases in VRN1 transcript levels in the leaves are associated with reduced responsiveness of CBF and COR genes to cold and with the end of the acclimation period. Therefore, delays in the induction of VRN1 and in the transition to the reproductive stage can extend the acclimation period and improve frost tolerance. These observations suggest that the vernalization and cold acclimation regulatory gene networks are interconnected.