A distinctive and essential feature of the vertebrate body is a pronounced left-right asymmetry of internal organs and the central nervous system. Remarkably, the direction of left-right asymmetry is consistent among all normal individuals in a species and, for many organs, is also conserved across species, despite the normal health of individuals with mirror-image anatomy. The mechanisms that determine stereotypic left-right asymmetry have fascinated biologists for over a century. Only recently, however, has our understanding of the left-right patterning been pushed forward by links to specific genes and proteins. Here we examine the molecular biology of the three principal steps in left-right determination: breaking bilateral symmetry, propagation and reinforcement of pattern, and the translation of pattern into asymmetric organ morphogenesis.