We focus in this chapter on how a new biophysicist obtains the insight to formulate an important biological hypothesis, to determine optimal experimental approaches, and to locate the needed facilities. The intent is not to expound on “the most important methods” and explain their inner workings, so that the new biophysicist can walk into a lab and attempt, for example, time-resolved electron microscopy of an H1N1 influenza virus invading a host cell. Books devoted to methods, as well as review articles and research experience courses are the proper source for such training. 1 We do delve into details and biophysical applications of atomic force microscopy, one of the twenty-first century’s most revolutionary experimental methods, in Chapter 19.