Multiple new agents to treat metastatic castration-resistant prostate cancer (mCRPC) have become available in recent years; however, the appropriate timing and sequencing of these agents have yet to be elucidated. Until accurate biomarkers become available to allow more focused therapeutic targeting for this population, treatment selection for men with mCRPC will continue to be driven largely by close assessment of patient-related factors and symptoms. Pain, as the predominant symptom of mCRPC, is often the focus when assessing progression and the need for a change in treatment. A myriad of other symptoms, including fatigue, impact on activities of daily living, sleep, and lower urinary tract symptoms, also affect men with mCRPC, and assessment of the composite of these symptoms provides an earlier signal for the need to adjust treatment. A number of tools are available for assessing symptoms in patients with advanced prostate cancer, but they are not routinely used, given their complexity and length. A new simplified questionnaire is proposed for the assessment of symptoms, beyond pain, to inform treatment decisions for men with mCRPC.