Type II DNA restriction and modification systems are ideally suited for analysis of mechanisms by which proteins specifically recognize unique DNA sequences. Each system is comprised of a unique DNA recognition site and two enzymes, which in those cases examined in detail, are comprised of distinct polypeptide chains. Thus, not only are the DNA substrates extremely well defined, but each system affords the opportunity to compare distinct proteins which interact with a common DNA sequence. This review will focus only on those Type II systems which have been examined in sufficient molecular detail to permit some insight into modes of specific DNA-protein interaction.