Prostate cancer (PCa) is an intractable disease, where diagnosis and clinical prediction of the disease course and response to treatment is compromised by the lack of objective and robust biomarker assays. In late stage metastatic disease, treatment options are limited, although it is recognized that some patients may benefit from immunotherapy and in particular vaccine therapy. However, research into biomarkers that correlate with the clinical outcome of immunotherapy has lagged behind vaccine development. Thus, proteomic tools are increasingly being utilized for the discovery of biomarkers which will allow us to make clinical decisions about patient treatment at an earlier stage and should aid in shortening the development time for vaccines. In this review we will summarize the various proteomic platforms used to investigate new biomarkers in PCa for better patient diagnosis, prognosis, patient stratification, treatment monitoring and clinical surrogate endpoints. We will discuss method limitations and highlight the key areas of research required for understanding the etiology of PCa.