Disease-free and overall survival have improved significantly for women diagnosed with early-stage breast cancer. At the same time, systemic therapy has only slightly enhanced long-term outcomes in advanced breast cancer, a disease that remains largely incurable. Several single-agent and combination chemotherapy approaches are available to women with hormone-insensitive advanced disease that may improve overall survival and progression-free survival, minimize symptoms and complications related to the disease, and improve overall quality of life. In addition, new cytotoxic and targeted agents have been recently introduced into practice and have improved both survival outcomes and quality of life. In this review, we will provide an update on commonly used chemotherapy-based regimens for the treatment of metastatic breast cancer, with a focus on tailoring therapy to different subtypes of the disease.