This text takes the reader on a guided tour through the philosophical and physical foundations of protein isolation. Aimed at a student readership, it will also be very useful to life science researchers faced with the task of isolating a protein for the first time. The logic of the overall approach to isolating a protein is explained and the physical principles of each separation method are made clear by the use of simple models and analogies, drawn from everyday experiences. The author's aim has been to deepen the readers' insight into protein isolation methods, so that they may tackle new problems and perhaps devise new approaches to old problems. Many of the methods described are drawn from the author's own research and are thus uniquely described here: examples are three-phase partitioning, non-linear electrophoresis, and a simple approach to buffer making.