Improved efficacy of treatment in metastatic castration-resistant prostate cancer (mCRPC) has dramatically increased the duration of exposure to potential treatment side effects. Given this, quality of life (QOL) considerations in treatment choice must be considered alongside efficacy. Moving forward, harmonization of QOL outcome measures, analytic methods, and reporting styles, as well as integration of assessments of contributing biological factors are needed to accelerate improvements in our understanding of the role of QOL for patients receiving systemic therapy.