Major advances have been achieved in the field of biologically based therapies for cancer in the last few years, and some of the recently approved molecular-targeted therapies are now being used in daily clinical practice. These molecular targets are also expressed in normal cells, which explains the different grades of toxicity, resulting from the disruption of normal cellular function. In general, targeted molecular therapies have good toxicity profiles, but some patients are exquisitely sensitive to these drugs and can develop particular and severe toxicities. In this article, we review the toxicity and safety of various small molecules and monoclonal antibodies used in solid tumors, with discussion of the pathophysiology, correlation with response, and strategies for prevention and management.