Radium-223 offers a well-tolerated and effective treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC) and symptomatic bone metastases. It is the first approved systematic alpha-therapy for cancer treatment since 2013. The use of radium-223 dichloride (Ra-223) for mCRPC with bone metastases is reviewed in this chapter. Radium-223 offers survival benefits, quality-of-life improvements, and reduced skeletal complications. Among the biomarkers for Ra-223 treatment, bone alkaline phosphatase and homologous recombination deficiency (HRD) stand out as promising tools for predicting response. Several patient cases with imaging studies are shown to demonstrate response to this therapy.