One of the major expectations from the use of humanized monoclonal antibodies in cancer therapy has been that of exploiting the specificity and sensitivity of the immune system to achieve selective therapeutic effects devoid of the often severe toxicity caused by chemotherapy. The tolerability of trastuzumab (Herceptin) as it emerged from the trials where the drug was used as a single agent or in combination with chemotherapy largely confirmed that expectation. Adverse events most frequently encountered include mild-to-moderate, transient effects related to administration of the first dose of trastuzumab. The incidence of severe or serious adverse effects attributable to trastuzumab was low. However, the occurrence of cardiac toxicity that was unexpectedly high, especially in patients previously or concomitantly treated with anthracyclines, could not be predicted on the basis of the putative mechanism of action of the antibody. The safety profile of trastuzumab is discussed here with a particular focus on cardiotoxicity and the issues relating to patient management during trastuzumab therapy.