The human epidermal growth factor receptor (HER) family of growth factor receptor tyrosine kinases (RTKs) plays an important role in the biology of many cancers. In breast cancer, HER2 and its homo- or heterodimerization with HER1 or HER3 are essential for cancer cell growth and survival. Patients overexpressing HER2 have a poor prognosis, which can be substantially improved upon HER2-targeted therapy using the monoclonal antibody trastuzumab. Lapatinib is a novel dual tyrosine kinase inhibitor, blocking HER1 and HER2 tyrosine kinase activity by binding to the ATP-binding site of the receptor's intracellular domain. This results in inhibition of tumor cell growth. The drug is relatively well tolerated in patients, with few and mostly low-grade adverse effects. In particular and unlike to trastuzumab, it has very little, if any, adverse effects on cardiac function. In patients with advanced HER2-positive breast cancer, lapatinib has shown substantial antitumor activity, particularly in combination with capecitabine upon progressive disease following standard therapy with antracyclines, taxanes, and trastuzumab. Ongoing and future studies will explore its role in the adjuvant therapy setting, in drug combinations other than capecitabine, and in the treatment of HER2-positive tumors other than breast cancer.