The use of fluorescence anisotropy to monitor protein-DNA interactions has been on the rise since its introduction by Heyduk and Lee in 1990. As a solution-based, true-equilibrium, real-time method, it has several advantages (and a few disadvantages) relative to the more classical methods of filter binding and the electrophoretic mobility shift assay (gel shift). This chapter discusses the basis for monitoring protein-DNA interactions using fluorescence anisotropy, as well as the advantages and disadvantages of the method, but the bulk of the chapter is devoted to experimental tips and guidance meant to augment existing reviews of the method. The focus is on the current primary use of the method: direct measurement of binding isotherms for protein-DNA interactions in vitro. A short summary of emerging applications of the method is also included.