Colorectal cancer remains a major cause of cancer mortality in the Western world. With a median age at presentation of 71, patients with metastatic disease are often elderly with significant co-morbidities. In addition, elderly patients are more likely to be undertreated and under-represented in clinical trials. Therefore, as the available data from clinical trials are scarce, the optimal treatment strategy for this group of patients has not been adequately defined. In the setting of metastatic colorectal cancer, the introduction of so called targeted agents has significantly improved outcomes in the context of randomized clinical trials, while at the same time increasing treatment options for such patients. This review focuses on the role of targeted therapies in elderly patients with metastatic colorectal cancer, with specific reference to toxicity and tolerability. It should be noted that studies reviewed herein will have mostly included fit elderly patients fulfilling specific inclusion criteria. The available data so far are limited but suggest that targeted agents have similar efficacy and tolerability in elderly fit patients when compared with younger ones, provided caution is exercised in specific high-risk sub-groups. Clearly, further studies aimed at this specific patient population using well-established geriatric end-points will hopefully identify those patients more likely to benefit and less likely to suffer severe side effects.