Background: Despite its importance, the structure and function of the placenta remains poorly understood. Objective: To describe the progress of theories regarding structure and function of the placenta from ancient to modern times. Design/Methods: Review of literature regarding history of the placenta. Results: In ancient times, virtually all recorded concepts of the placenta described it as animistic or possessing mind or spirit. For example, the ancient Egyptians believed that the placenta contains part of the child’s soul, which will only emerge if treated well. The Royal Placenta used to be carried in ceremonial procession as a standard before the Pharaoh. Each Pharaoh had an official ‘’Opener of the King’s Placenta”. The transition from animistic to functionality began with the Greeks. Diogenes of Apollonia (480 BC) is credited with the idea that the placenta is an organ of fetal nutrition. Hippocrates (460-370 B.C.) believed that fetus ‘sucks nutrition from ‘uterine paps’. Aristotle (384-322 BC) was the first to postulate delivery of nutrition through the umbilical cord. The Renaissance marked the beginning of rapid progress in understanding the structure and function of the placenta. J.C. Arantius (1530-1589) was the first to describe separate maternal-fetal circulation in dissected specimens. In the following century, John Mayow (1643-1679) proposed that the placenta was the respiratory organ of the fetus and shifted the concept of the placenta from HeparUterinumto PulmoUterinus. The 19th century witnessed a fast growth in understanding the structure of the placenta. William Hunter was the first to give a sophisticated description of the structure of the placenta. Biscoff (1842) made many contributions to the understanding of placental barrier. Charles Sedwig Minot (1891) published a detailed description of the placentas of different species. In the 20th century, the placenta was recognized for the first time as an endocrine organ and the new focus became the transfer of solutes across the placenta. Despite this journey of evolving understanding of the complexities of the placenta, significant knowledge gaps remain in understanding placental functions. The Human Placental Project sponsored by National Institute of Health (NIH) described eloquently the need for continuing research in this field. “The Placenta is the least understood human organ and arguably one of the most important…The Human Placental Project, would make substantial inroads”. Conclusions: Our understanding of the human placenta has progressed from an animistic tissue to a multi-functional fetal organ. The NIH’s Human Placental Project should continue to improve our knowledge of this mysterious “least understood organ”.