Human epidermal growth factor receptor 2 (HER2)-positive breast cancers account for approximately 15 to 20% of breast cancer diagnoses. Historically, HER2-positive breast cancers had been associated with poorer prognosis. The addition of HER2-targeted agents to treatment regimens has significantly improved outcomes for patients with HER2-positive breast cancer. Despite this, relapses continue to occur in about 20% of patients. Newer therapeutic strategies are needed. The role of immunotherapy in the treatment of HER2-positive breast cancer is currently under clinical investigation. This article will focus on the clinical trial data evaluating immune checkpoint inhibitors, including pembrolizumab, atezolizumab, avelumab, durvalumab, and nivolumab in the treatment of HER2-positive breast cancer. The incorporation of immunotherapy in the treatment of HER2-positive breast cancer is a reasonable strategy. Clinical trials of checkpoint inhibitors with HER2-targeted agents show clinical activity in HER2-positive breast cancer tumors that are programmed cell death-ligand 1 (PD-L1) positive and also when used as an earlier line of therapy in the metastatic setting. Treatment of HER2-positive breast cancer with immunotherapy and HER2-targeted agents warrants continued clinical investigation.