This Review highlights current areas of controversy and development in the field of transperineal permanent prostate seed implantation brachytherapy (PPI), in particular the technological evolution of PPI treatment planning that has led to intra-operative treatment planning and execution, the use of MRI spectroscopy and ultrasonography to target intraprostatic tumor foci, and the introduction of (131)Cs as a new PPI isotope. Here we present a comprehensive review of mature data for PPI monotherapy and PPI combined with supplemental external beam radiation therapy, and a critical discussion of issues pertinent to supplemental EBRT. We also present our current policies in the treatment of prostate cancer at the University of California, San Francisco.