Gemcitabine, a pyrimidine nucleoside antimetabolite, is one of the most promising new cytotoxic agents. The drug has shown activity in a variety of solid tumors, and has been approved for the treatment of non-small cell lung cancer, pancreatic, bladder, and breast cancer. Recent data showed that gemcitabine is also active against ovarian cancer. Gemcitabine has a good toxicity profile, with myelosuppression being the most common side effect, while non-hematological events are relatively uncommon. The low toxicity profile makes the drug a valid option for unfit and elderly patients. Due to the synergistic activity with other chemotherapeutic compounds, mainly cisplatinum, several trials have been conducted to evaluate the efficacy and tolerability of gemcitabine in combination with other cytotoxic agents. Current clinical trials are evaluating the role of gemcitabine in combination with new targeted therapies.