The human epidermal growth factor receptor (HER) family of receptor tyrosine kinases plays an important role in the biology of many cancers. In breast and gastric cancer, and maybe also additional tumor types, HER2 and its homo- or heterodimerization with HER1 or HER3 are essential for cancer cell growth and survival. Breast cancer patients overexpressing HER2 have a poor prognosis, which can be substantially improved upon HER2-targeted therapy using the monoclonal antibody trastuzumab. Lapatinib is a dual tyrosine kinase inhibitor (TKI), blocking HER1 and HER2 tyrosine kinase activity by binding to the ATP-binding site of the receptor's intracellular domain. This results in the inhibition of tumor cell growth. In patients, the drug is relatively well tolerated with mostly low-grade adverse effects. In particular and unlike to trastuzumab, it has very little, if any, adverse effects on cardiac function. In 2007, lapatinib has been approved in combination with capecitabine in patients with advanced HER2-positive breast cancer upon progressive disease following standard therapy with anthracyclines, taxanes, and trastuzumab. In 2010, the approval was extended to the treatment of postmenopausal women with advanced, hormone receptor- and HER2-positive breast cancer, for whom hormonal therapy is indicated. Ongoing and future studies will explore its role in the (neo)adjuvant therapy setting, in further drug combinations as well as in the treatment of HER2-positive tumors other than breast cancer.