How can proteins bind DNA in the cell nucleus, where it is present in form of chromatin, tightly wrapped around histones and therefore mostly inaccessible? Recently, several studies began to uncover the various strategies used by DNA-binding proteins to solve this problem. In a Cell "Leading Edge review," Alicia Michael and Nico Thomä look at these findings and highlight general principles that aim to help predict how a protein recognizes a specific stretch of DNA, even when "hidden" in chromatin.