We report a Rh-catalyzed method for the C-5 selective C-H iodination of naphthoquinones and show that complementary C-2 selective processes can be achieved under related conditions. C-C bond forming derivatizations of the C-5 iodinated products provide a gateway to previously inaccessible A-ring analogues. The present study encompasses the first catalytic directed ortho-functionalizations of simple (non-bias) naphthoquinones. The strategic considerations outlined here are likely to be applicable to C-H functionalizations of other weakly coordinating and/or redox sensitive substrates.