Historically, the treatment of prostate cancer has required little anatomic information beyond the location of the prostate gland and adjacent seminal vesicles. Radiation therapy has classically been prescribed to the whole prostate due to the high frequency of multifocal cancer in surgical specimens and the inability to localize the precise boundaries of individual tumor foci on imaging. The development of prostate magnetic resonance imaging (MRI) and positron emission tomography (PET) using prostate-specific radiotracers has ushered in an era in which radiation oncologists are able to localize and focally dose-escalate high-risk volumes in the prostate gland. Recent phase III data have demonstrated that incorporating focal dose escalation improves biochemical control without significantly increasing toxicity. However, many questions remain regarding the optimal target volume definition and prescription strategy to implement this practice. In this review we summarize the currently available literature on image-based focal target delineation with MRI and PET. Our review includes a summary of the available data on anatomic patterns of spread to inform clinical judgement for the definition of clinical target volumes. Key knowledge gaps are identified and suggestions for novel implementation strategies are provided.