Prostate cancer encompasses a biological continuum from a slow-growing indolent tumour to a highly aggressive and potentially fatal form. A major challenge faced daily by physicians is to identify men with localized prostate cancer who are at high risk of dying from the disease, in order to maximize disease control and survival, without overtreating men who are likely to die from comorbidities. Treatment selection in patients with localized prostate cancer should be guided not only by patient-related factors (e.g. age and comorbidities), but also by cancer-related parameters (clinical stage, biopsy grade and preoperative prostate-specific antigen [PSA]) that enable patients to be classified as low, intermediate, or high risk for unfavourable outcomes. Surgery alone will only cure a fraction of high-risk patients. Instead these patients typically need a pro-active multimodal approach comprising a combination of surgery, radiotherapy and/or hormonal deprivation. The place of chemotherapy in the adjuvant or neoadjuvant setting in this patient group needs to be evaluated in clinical trials.