Triple-negative breast cancer (TNBC) types with poor prognosis are due to the absence of estrogen receptors, progesterone receptors and HEGFR-2. The lack of suitable therapy for TNBC has led the research community to turn toward epigenetic regulation and its protagonists that can modulate certain oncogenes and tumor suppressors. This has opened an important new field of therapy using epi-drugs, in preclinical and clinical trials. The epi-drugs are natural or synthetic molecules capable of inhibiting or modulating the activity of epigenetic proteins such as DNA methyltransferases, modulating the expression of interferon microRNAs, as well as histone methyltransferases, demethylases, acetyltransferases and deacetylases. This review investigated the epi-drugs used in the treatment of TNBC.