Approximately 20 molecular targeted therapies, mainly monoclonal antibodies and tyrosine kinase inhibitors, have been approved for the treatment of various cancers. They are being increasingly investigated in combination in clinical trials. We review the rationale for combining molecular targeted therapies and the results of clinical trials to date. There have been some exciting clinical results with some combinations, for example, lapatinib/trastuzumab or bevacizumab/trastuzumab in HER2-positive metastatic breast cancer, whereas other potential combinations have provided disappointment, for example, cetuximab or panitumumab in combination with bevacizumab/chemotherapy in first-line treatment of metastatic/advanced colorectal cancer. Therefore, at this point no general guidance to study such combinations can be derived.