Since the establishment of docetaxel as first-line chemotherapy for metastatic castration-resistant prostate cancer significant advancements have been made in the management of this disease. Clinical trials have investigated agents for use prior to docetaxel, in combination with docetaxel and agents for second-line treatment for patients who have progressed despite docetaxel. In addition, several new agents have been developed and clinically investigated in the fields of hormonal, cytotoxic, targeted and immune therapy, providing options either side of first-line chemotherapy. As a result of this considerable research activity, three new therapies; cabazitaxel, sipuleucel-T and abiraterone acetate, have each demonstrated improvement in overall survival in phase III trials and have been approved by the US Food and Drug Administration. With so many new therapies now available and in the pipeline, the management of metastatic castration-resistant prostate cancer is undergoing a significant and positive change. This article discusses current and future options for second-line therapy in metastatic castration-resistant prostate cancer, providing insight into the potential roles of these new treatment options in the Australian clinical setting.