Patients with cancer show variable levels of immunosuppression at the time of the presentation, and cytotoxic antineoplastic therapy is the primary contributor to the clinical immunodeficiency often observed during the course of the disease. In both hematological and solid tumors, this phenomenon is primarily related to the T-cell depletion associated with inhibition of dendritic cell ability to induce both primary and secondary T- and B-cell responses. Complete restoration of immunocompetence following antineoplastic therapy implicates the progressive recovery of various cell subpopulations, and it is a complex process that also depends on the type, the dose, the scheduling, and the associations of the employed drugs. In the era of target therapies, several antiangiogenic drugs are increasingly used in combination with standard chemotherapy in the treatment of advanced solid tumors. Their clinical efficacy has been recently related not only to the specific antiangiogenic properties but also to an indirect hypothetical effect on the host immune system. In the present work, we have reviewed the most recent information regarding (1) the capacity of standard antineoplastic therapy to induce and maintain an immunodeficiency in patients with solid tumors and (2) the influence of the antiangiogenic treatment in association with standard chemotherapy on lymphocyte and dendritic cell subsets and the possible resulting additional antitumor mechanism.