The birth of Louise Brown in 1978 marks the beginning of IVF, yet it was preceded by numerous inventions and discoveries that enabled IVF in the manner conducted these days. In this chapter, we will review the major milestones, starting with the discoveries made during Renaissance that changed dogmas on reproduction that dated back to the times of the Greeks and Romans. These included the discovery of sperm, the understanding of the process of fertilization, and the pivotal role that the fallopian tubes have in it. Later, with the realization that women with blocked tubes may not conceive, major efforts were made to develop a surgical solution that led up to the understanding that this problem calls for a completely new type of solution, the creation of life outside the body to bypass the blockage. The development of IVF was and still is accompanied not only by overcoming technical and scientific barriers but also with walking on a fine thread between what the public as well as the religious and civilian governing bodies will consider a practical solution to an acute public need and an immoral slippery slope that may lead to societal disintegration. Some of these challenges still accompany clinical day to day practice in IVF as well as the challenges with the introduction of emerging technologies in ART.