The role of the immune system in tumor dormancy is now well established. In several experimental models it is possible to induce tumor dormancy in immunocompetent hosts by prior immunization against tumor cells. Equilibrium between immune response and tumor cells leads to long-term tumor dormancy. This equilibrium is also observed early in tumor development and adaptive immunity may help contain tumor outgrowth. However, after variable times, tumor dormancy ends and the disease progresses. As the immune response remains active the tumor cells presumably escape dormancy by becoming resistant. Due to the extreme difficulty of isolating dormant tumor cells from patients, such mechanisms are poorly understood. However, experimental models have shown that dormant tumor cells may overexpress B7-H1 and B7.1, and inhibit CTL-mediated lysis. These cells resist apoptosis by methylating SOCS1, and by paracrine production of cytokines. The presence of immunoescape mechanisms in tumor cells from relapsing patients also suggests that the immune equilibrium which maintained dormancy has broken down. Identification of such mechanisms would offer new leads to favor the immune balance, and thus to clear minimal residual disease from patients.