This chapter describes Charles Darwin’s physical and intellectual journey to the conception of his masterpiece, Origin of Species. Here, the voyage of the HMS Beagle is recounted, and Darwin’s pre-Origin publications are described, including Journal of Researches, which became The Voyage of the Beagle. Then, the arguments posed in Origin of Species and Descent of Man are presented. This chapter discusses those aspects of Darwin’s major writings that are not addressed and that Darwin could not know. First and foremost, Darwin did not have a mechanism by which inheritance of parental characteristics or the variation of those characteristics occurs. This was later found in the work of Gregor Mendel in his theories of particulate inheritance. Darwin was aware of but did not explicitly discuss the evolution of microbial organisms, even though he corresponded with prominent microbiologists of the day, including Louis Pasteur, Robert Koch, and Christian Ehrenberg. The reasons for this are briefly discussed.