Since the advent of hybridoma technology, dating back to 1975, monoclonal antibodies have become an irreplaceable diagnostic and therapeutic tool for a wide array of human diseases. During the last 15 years, several monoclonal antibodies (mAbs) have been approved by FDA for cancer therapy. These mAbs are designed to (1) activate the immune system against tumor cells, (2) inhibit cancer cell-intrinsic signaling pathways, (3) bring toxins in the close proximity of cancer cells, or (4) interfere with the tumor-stroma interaction. More recently, major efforts have been made for the development of immunostimulatory mAbs that either enhance cancer-directed immune responses or limit tumor- (or therapy-) driven immunosuppression. Some of these antibodies, which are thought to facilitate tumor eradication by initiating or sustaining a tumor-specific immune response, have already entered clinical trials. In this Trial Watch, we will review and discuss the clinical progress of the most important mAbs that are have entered clinical trials after January 2008.