From the earliest observations of human chromosomes in the late 1800s to modern day next generation sequencing technologies, much has been learned about human cancers by the vigorous application of the techniques of the day. In general, resolution has improved tremendously, and correspondingly the size of the datasets generated has grown exponentially such that computational methods required to handle massive datasets have had to be devised. This chapter provides a brief synopsis of the evolution of such techniques as an introduction to the subsequent chapters that provide methods and applications, relevant to research, and clinical diagnostics.