Currently, the debate about the nature of the human mind is taking new directions through the development of several studies investigating the location of brain functions in the field of neuroscience. These studies have been contributing to a better understanding of the neural substrates of mental functions and the etiology of various mental disorders. However, the knowledge developed by neuroscience did not occur abruptly. Indeed, the study of mind-brain relationship is not new. From pre-history to the present day, various different forms types of inquiries were made about the possible materiality and location of human mental functions. This paper presents, in a historic manner, how prehistoric populations, as well as early civilizations located in Egypt, Mesopotamia, India, and China and Greece developed and employed concepts related to the soul, mind and human brain.