Vascular leukocytes are a unique population of CD45+ VE-cadherin+ cells with diverse functions. VLCs are capable of antigen presentation, as well as formation of endothelial-like structures in vitro and in vivo. VLCs are largely present among CD45+ cells infiltrating human ovarian carcinomas and are highly represented in the beta-defensin-VEGF-ID8 syngenic mouse model. Vascular leukocytes are a new and promising novel therapeutic target for anti-angiogenic therapy. Their unique mechanism merits thorough and extensive exploration in the future.