Prostate cancer is a significant public health problem, and the most commonly diagnosed cancer in the USA. The long natural history of prostate cancer, the presence of a serum biomarker that can be used to detect very early recurrences, and the previous identification of multiple potential tissue-specific target antigens are all features that make this disease suitable for the development of anti-tumor vaccines. To date, many anti-tumor vaccines have entered clinical testing for patients with prostate cancer, and some have demonstrated clinical benefit. DNA vaccines represent one vaccine approach that has been evaluated in multiple preclinical models and clinical trials. The safety, specificity for the target antigen, ease of manufacturing and ease of incorporating other immune-modulating approaches make DNA vaccines particularly relevant for future development. This article focuses on DNA vaccines specifically in the context of prostate cancer treatment, focusing on antigens targeted in preclinical models, recent clinical trials and efforts to improve the potency of these vaccines.