The possibility of using the immune system of patients to control tumor outgrowth in a therapeutic setting has always been highly appealing to both clinicians and researchers. However, although cancer cells express tumor-associated antigens that can be targeted by T-cells, clinical trials suggest that the induction of specific immune responses per se may be insufficient to achieve clinical goals. Based on these trial data, in addition to experimental data revealing the complexity of mechanisms controlling immune responsiveness, a reassessment of immunotherapy procedures is underway. As a result, a second generation of antitumor treatments that includes reagents of potential pharmaceutical relevance is being developed. In this review, the most recent literature addressing issues related to immunotherapy for solid tumors is discussed.