Targeting of the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon gene (STING) innate immune response pathway has emerged as a promising therapeutic direction in breast cancer. cGAS is a cytosolic enzyme that senses double-stranded DNA and activates STING, promoting a downstream antitumor response via production of type I interferons, enhanced CD8+ T cell infiltration, and other immunomodulatory effects. STING can be therapeutically targeted with direct agonists such as cyclic dinucleotides or indirectly targeted with conventional breast cancer therapies such as radiotherapy, cytotoxic chemotherapy, and inhibitors of poly (ADP-ribose) polymerase. In preclinical models, therapeutic efficacy may be enhanced in combination with other immunotherapies, such as anti-programmed death 1/ligand 1 or cancer vaccines. Here, we review preclinical evidence in support of targeting STING in breast cancer either as monotherapy or in combination with other therapies. We also summarize ongoing clinical trials, dosing paradigms, and unique considerations for targeting STING across the different histologic subtypes of breast cancer.