Breast cancer is one of the most common cancers worldwide. Various therapies, such as hormonal therapy, chemotherapy, and biologic therapies, can increase cure rates in the early-stage setting and improve survival and quality of life in specific advanced-disease settings. For advanced disease, the optimal timing, type, and combination of drugs remain to be defined. Gemcitabine is a newer agent with a unique mode of action that involves DNA chain termination and mechanisms that result in self-potentiation. This results in a broad spectrum of activity in many types of solid tumors including breast cancer. As a single agent, gemcitabine yields response rates ranging from 14%-37% as first-line therapy for advanced breast cancer and 23%-42% as salvage therapy. However, these were small studies with large confidence intervals around all the indices of benefit including response rate, response duration, and time to disease progression. Gemcitabine was associated with higher response rates when used in combination with other agents. The side-effect profile of gemcitabine has been favorable compared to that of commonly used cytotoxic drugs, and includes myelosuppression and fatigue, with a notable absence of alopecia and gastrointestinal symptoms. Larger ongoing studies will help define the utility of gemcitabine in advanced breast cancer