This essay explains the importance of the limitations imposed by the laws of the brain on our expedience of art, when looking at paintings. The first part describes the importance of painted masterpieces for human culture and the history of art from a neural point of view. Creativity is an essential communication tool revealing the self. Art, beauty, mind, soul, emotion and taste will be addressed from a neural perspective. The second part explores some essential functions of the brain involved in cognitive perception of art. The physiology of the self, consciousness, learning, memory, creativity and bias will be discussed. We all select our own masterpieces following our emotions, the self, domain knowledge and our private acceptance of social norms, which educate our personal taste. Connoisseurship, aesthetics, the market, authenticity and peer review are examined in the third part; as well as a short survey of masterpieces and Contemporary art to illustrate how great artists’ works exploited unconsciously the laws of the brain.