Scientific interest in the palmar, plantar, and digital flexion creases has been related mainly to their aberrations in numerous congenital malformations and other medical disorders. Understanding of crease embryonal development is a prerequisite to the estimation of their potential significance in medical practice. While the timing of development of the flexion creases has now been established, their origin is less well understood. Both primary genetic determination and development secondary to flexion function have been suggested as the mechanisms underlying the crease development. The evidence offered has been mostly indirect, related to the timing of the onset of the fetal hand movement and the crease aberrations in malformed hands and fingers. More detailed studies, preferably including experimental designs in nonhuman fetuses, will be necessary to resolve the question of the origin of the flexion creases. In the meantime, it seems reasonable to assume that the flexion creases develop under genetic influences, in close morphologic relationship to the fetal volar pads. Early genetic and environmental factors causing hand malformations and alterations of the form or function of the hand, and occurring prior to the fetal crease development, may affect the developing flexion creases. The close correspondence between the appearance of the flexion creases and hand and digital movement (which, in turn, is associated with joint formation and muscular function) suggests that the same earlier factors are responsible for both crease development and flexion movement.