Theorists have long speculated on the mechanisms driving directed and spontaneous cell polarization. Recently, experimentalists have uncovered many of the mechanisms underlying polarization, enabling these models to be directly tested. In the process, they have demonstrated the explanatory and predictive value of these models and, at the same time, uncovered additional complexities not currently explained by them. In this review, we discuss some of main theories regarding cell polarization and highlight how the intersection of mathematical and experimental biology has yielded new insights into these mechanisms in the case of budding yeast and eukaryotic chemotaxis.