During the past decade, significant progress has been made in understanding the interactions between the immune system and cancer. The re-emergence of cancer immunosurveillance and immunoediting concepts has provided an understanding of several immunologic markers that are associated with cancer progression and prognosis. Recent studies have attempted to define the critical role of tumor infiltration by lymphocytes as a reflection of a tumor-related immune response. More recently, there has been an improved ability to demonstrate distinct subsets of tumor-infiltrating lymphocytes (TILs) in different tumor compartments. Several of these studies indicate that the presence of TILs may be associated with improved clinical outcome in several human cancers. However, this improved clinical outcome is dependent upon the intratumoral balance and quality of TILs, or infiltration of regulatory T cells or myeloid-derived suppressor cells. Immunologic markers have an important role in demonstrating intermediate end points of a therapeutic intervention and ultimately may be useful in predicting clinical outcomes. These markers are important to the development of successful immunotherapy strategies in cancer.