Marcello Malpighi studied chick embryos with microscopes in Italy during the seventeenth century. Trained as a medical doctor, he was among the first scientists to use the microscope to examine embryos at very early stages. Malpighi described early structures in chick embryos, and later scientists used his descriptions to help develop the theory of preformationism.

In "Selective Growth Stimulating Effects of Mouse Sarcoma on the Sensory and Sympathetic Nervous System of the Chick Embryo," Rita Levi-Montalcini and Viktor Hamburger explored the effects of two nerve growth stimulating tumors; mouse sarcomas 180 and 37. This experiment led to the discovery that nerve growth factor was a diffusible chemical and later to discoveries that the compound was a protein. Although this paper was an important step in the discovery of nerve growth factor, the term "nerve growth factor" was not used in this paper. It was instead referred to as a "growth promoting agent." The discovery of nerve growth factor earned Levi-Montalcini and Stanley Cohen, who also discovered epidermal growth factor, the 1986 Nobel Prize in Physiology or Medicine.

The developmental stages of the chick embryo were examined by Viktor Hamburger and Howard L. Hamilton in "A Series of Normal Stages in the Development of the Chick Embryo," published in the Journal of Morphology in 1951. These stages were published to standardize the development of the chick based on varying laboratory conditions and genetic differences. The stages Hamburger and Hamilton assigned were determined by the visible features of the chick embryo. The first stage begins just prior to the primitive streak, with the formation of the embryonic shield, and the final stage, forty-six, ends at the hatching of the chick.