Over a long period of more than a century, breeding and improvements in cropping systems have led to a constant increase in grain yield in barley. Due to its autogamous propagation, commercial barley varieties are normally true inbred lines or doubled haploid lines normally having completely homozygous genomes. Hybrid breeding in autogamous cereals such as barley, however, is still in its infancy. This chapter describes the principles of heterosis in barley and its potential for yield enhancement. The chapter explains the potential of hybrid breeding in winter barley and examines the challenges associated with broadening the genetic basis for heterosis in winter barley. The chapter describes the cytoplasmic male sterility system for hybrid seed production in barley and looks at the environmental and genetic effects of hybrid breeding on the stability of cytoplasmic male sterility.