5-Hydroxymethylcytosine (hmC), the sixth base of the mammalian genome, is increasingly recognized as an epigenetic mark with important biological functions. We report engineered, programmable transcription-activator-like effectors (TALEs) as the first DNA-binding receptor molecules that provide direct, individual selectivities for cytosine (C), 5-methylcytosine (mC), and hmC at user-defined DNA sequences. Given the wide applicability of TALEs for programmable targeting of DNA sequences in vitro and in vivo, this provides broad perspectives for epigenetic research.