The most asymmetrically shaped and behaviorally lateralized of all the vertebrates, the flatfishes are an endless source of fascination to all fortunate enough to study them. Although all vertebrates undergo left–right asymmetric internal organ placement during embryogenesis, flatfish are unusual in that they experience an additional period of postembryonic asymmetric remodeling during metamorphosis, and thus deviate from a bilaterally symmetrical body plan more than other vertebrates. As with amphibian metamorphosis, all the developmental programs of flatfish metamorphosis are ultimately under the control of thyroid hormone. At least one gene pathway involved in embryonic organ lateralization (nodal-lefty-pitx2) is re-expressed in the larval stage during flatfish metamorphosis. Aspects of modern flatfish ontogeny, such as the gradual translocation of one eye to the opposite side of the head and the appearance of key neurocranial elements during metamorphosis, seem to elegantly recapitulate flatfish phylogeny. This chapter highlights the current state of knowledge of the developmental biology of flatfish metamorphosis with emphases on the genetic, morphological, behavioral, and evolutionary origins of flatfish asymmetry.