When Folkman first suggested a theory about the association between angiogenesis and tumor growth in 1971, the hypothesis of targeting angiogenesis to treat cancer was formed. Since then, various studies conducted across the world have additionally confirmed the theory of Folkman, and numerous efforts have been made to explore the possibilities of curing cancer by targeting angiogenesis. Among them, anti-angiogenic gene therapy has received attention due to its apparent advantages. Although specific problems remain prior to cancer being fully curable using anti-angiogenic gene therapy, several methods have been explored, and progress has been made in pre-clinical and clinical settings over previous decades. The present review aimed to provide up-to-date information concerning tumor angiogenesis and gene delivery systems in anti-angiogenic gene therapy, with a focus on recent developments in the study and application of the most commonly studied and newly identified anti-angiogenic candidates for anti-angiogenesis gene therapy, including interleukin-12, angiostatin, endostatin, tumstatin, anti-angiogenic metargidin peptide and endoglin silencing.