In this review, we (i) present the notion of homologous recombination deficiency and its evaluation methods, (ii) detail the PARP inhibitor clinical trials in breast cancer, (iii) briefly describe the mechanisms to PARP inhibitors resistance, and (iv) discuss some strategies currently under evaluation to enhance the therapeutic index of PARP inhibitors in breast cancer. The gene discussed is PARP1; the disease is breast carcinoma.