Current therapies for metastatic ovarian carcinoma are based on surgical debulking followed by chemotherapy. After more than three decades implementing treatments that selectively target the tumor cell, the 5-year survival rate for metastatic ovarian cancer patients is still lower than 30%. Novel strategies are therefore urgently needed to complement classical treatments for this malignancy. Recently, leukocytes in the ovarian cancer microenvironment such as regulatory T cells and immature pro-angiogenic/tolerogenic myeloid cells have been demonstrated to play a fundamental role in tumor progression. This review focuses on our recent understanding of the potential of eliminating and/or modulating the phenotype of these leukocytes in vivo and in situ as a novel intervention to complement standard ovarian cancer treatments. The significant effects of targeting these crucial microenvironmental players on cancer vascularization, local tumor growth, distal metastatic spreading and spontaneous anti-tumor immune responses are discussed.