A benefit of anti-angiogenic drugs is improved tumor immune tolerance. Regulatory T cells (Tregs) in the tumor microenvironment mediate tumor immune tolerance and anti-angiogenic drugs not only indirectly affect Tregs via dendritic cells (DCs) and myeloid-derived suppressor cells (MDSCs) but they can also act directly on Tregs causing immunosuppression. Specifically, these drugs may induce differentiation and chemotaxis and reduce the number and function of Tregs by targeting vascular endothelial growth factor receptor 2 (VEGFR-2) and neuropilin-1 (NRP-1) on the cell surface. Recently, anti-angiogenic drugs have been documented to promote a new way of thinking about tumor immunotherapy: clinical application of Tregs and related immunosuppressive molecules may be promising targets for synergistic tumor immunotherapy.