The identification of novel molecular targets has paved the way for new treatment options in cancer patients. A number of agents targeting molecules that are crucial both for the tumor and its microenvironment have already been approved by the U. S. Food and Drug Administration for clinical use. The monoclonal antibodies and the small molecule kinase inhibitors constitute two major classes of targeted therapeutic agents, which have apparently different mechanisms of action, toxicity profiles, routes of administration, timing and dosing. Moreover, individual differences in genes regulating the distribution and metabolism of targeted agents evidently influence treatment outcomes. Data regarding the immune-and tumor microenvironment-modulatory properties of most of these agents are either obscure or controversial, as well. Therefore, preclinical animal and human studies that aim to identify the immunological, biological and the pharmacological properties of these novel classes of agents that also employ recent developments in pharmacogenomics and proteomics are warranted.