Inhibition of the immune checkpoint regulator programmed cell death ligand-1 (PD-L1), and its receptor, programmed death-1 (PD-1), has significantly altered the therapeutic landscape of breast cancer, providing durable responses in selected patients. Several PD-1/PD-L1 inhibitors have been evaluated as monotherapy or in combination with chemotherapy or targeted agents, mainly in triple-negative breast cancer (TNBC), due to higher rates of immune cell infiltration and higher expression of genes associated with cytokines and cytokine receptors and immune cells in this subtype compared to non-TNBC tumors. Based on the results of the IMpassion130 and KEYNOTE-355, first-line treatment with atezolizumab or pembrolizumab, respectively, in combination with chemotherapy, provided clinical benefit to patients with advanced PD-L1-positive TNBC. PD-1/PD-L1 inhibitors have also been evaluated in combination with chemotherapy or targeted agents in estrogen receptor (ER)+/HER2− and HER2+ breast cancer subtypes, providing minimal clinical benefit. Despite the significant clinical benefit in selected populations, only a proportion of patients with advanced breast cancer present durable responses, while most either demonstrate primary resistance or progress a few months after initiation of treatment. To date, PD-L1 expression and microsatellite instability (MSI)-high status are being used to select patients with advanced breast cancer for treatment with PD-1/PD-L1 inhibitors. Since immune checkpoint inhibitors are treatments that might be associated with severe toxicities, further research to identify biomarkers for improved patient selection is warranted.