Triple-negative breast cancer (TNBC) is an aggressive subgroup of human breast cancer, which is characterized as estrogen receptor (ER) negative, progesterone receptor (PR) negative, and human epidermal growth factor receptor 2 (HER2) negative. TNBC is the most difficult breast cancer subgroup to treat, due to its unresponsiveness to current clinical targeted therapies, high rate of recurrence, and poor prognosis. Thus, there is an urgent medical need to identify therapeutic targets and develop more effective stratified medicine for the treatment of TNBC. Here we review the potential therapeutic targets for TNBC based on its intrinsic subtype. We also review the aberrant activated signals found in different subgroups of TNBC, including androgen receptor (AR) and PI3K/AKT/mTOR, Notch, Wnt/beta-catenin, Hedge-hog, and TGF-beta signaling pathways, which play essential roles in multiple development stages of TNBC. The careful analysis of these signaling pathways and therapeutic targets would have significant impact on the drug development and clinical trials, leading to effective therapies for this deadly disease.