Significant progress has recently been achieved in designing strategies to stimulate the generation of tumor-specific immune effector cells through the use of tumor vaccines and cytokine therapies [1, 2, 3]. However, a frequently overlooked determinant of the success of immunotherapy relates to the ability of immune effector cells to efficiently gain access to tumor tissues. Lymphocytic infiltration within tumor tissues is under local microenvironmental control and is a prerequisite for the initiation of lytic cascades which occur as a consequence of direct physical contact between malignant cell targets and immune effector cells. Here we review evidence that tumor microvessels serve as a barrier to lymphocyte recruitment, thereby allowing malignant cells to evade immune-surveillance mechanisms. Additional issues to be discussed include current information regarding the cooperative mechanisms orchestrating lymphocyte migration across the vascular barrier in normal and malignant tissues, and experimental approaches that are under investigation to actively promote lymphocyte recruitment to tumor sites.