During mammalian meiosis, double-strand breaks are deliberately made throughout 
the genome and then repaired, leading to the exchange of genetic material 
between copies of chromosomes. How the locations of breaks are specified was 
largely unknown until a fortuitous confluence of statistical genetics and 
molecular biology uncovered the role of PRDM9, a DNA binding protein. Many 
properties of this protein remain mysterious, however, including how it binds to 
DNA, how it contributes to male infertility-both in humans, and in hybrid 
mice-and why, in spite of its fundamental function in meiosis, its binding 
domain varies extensively among humans and across mammals. We present a brief 
summary of what has recently been learned about PRDM9 in different fields, 
focusing on the puzzles yet to be resolved.