Resistance to therapies and disease recurrences after surgery or treatment are common challenges in breast cancer management in clinic. Active immunotherapy using human epidermal growth factor receptor 2 (HER2)-targeted vaccines represents an attractive option in combating breast cancer. Different HER2-derived vaccines have been developed over the years. Many clinical trials have been carried out in evaluating HER2-based vaccines. The authors reviewed current literature on HER2-based vaccines in clinical trials. The trials covered in this mini-review represent some of the major trials published in the past 20 years regarding the clinical use and test of HER2 vaccines. Their focus is on trials using HER2 peptide vaccines as the majority of clinical trials initiated or published used HER2 peptide-based vaccines. Findings from combination therapy trials of HER2 peptide vaccines with other treatment modalities are also presented.