Advances in the engineering of peptides, adjuvants and delivery systems have renewed the enthusiasm for peptide-based vaccination regimens in the setting of cancer, and there are a variety of clinical trials being conducted by pharmaceutical companies based on the use of peptides. The challenges to successful cancer immunotherapy are common to all immunotherapeutic strategies and not unique to peptide-based vaccination regimens. This review will describe the advances in the identification, design and delivery of peptides, the challenges to successful immunotherapy and will discuss potential options for the future.