Lonidamine belongs to a new class of antineoplastics agents, since it does interfere with cell energy processes. When administered as single agent in metastatic breast cancer, it produces moderate therapeutic effects. The pattern of toxicity includes myalgias, asthenia, testicular pain, and gastrointestinal discomfort. No myelosuppression was demonstrated in phase I-II studies. Since the peculiar mechanism of action and side effects are not overlapping with those of standard chemotherapeutic agents, combination of lonidamine with chemotherapy is currently under investigation in advanced breast cancer. Moreover, the potentiation of radiotherapy by lonidamine could be of interest in palliating symptomatic lesions from breast cancer.