Recent advances in anti-angiogenic inhibitors targeting the VEGF/VEGFR axis have significantly improved the treatment of cancers and retinal diseases. VEGF and its receptors (VEGFRs) are crucial in regulating angiogenesis, both physiological and pathological. Anti-angiogenic drugs inhibit VEGF/VEGFR interactions, VEGFR tyrosine kinase (TK) activity, or downstream signaling pathways to prevent new blood vessel formation. These drugs include monoclonal antibodies, fusion proteins, and small molecules. Monoclonal antibodies like bevacizumab, ranibizumab, and aflibercept are effective in treating cancers and retinal diseases, while small molecules such as sorafenib, sunitinib, and cabozantinib target VEGFR TKs and downstream signaling pathways. These drugs have shown clinical benefits but also pose challenges such as toxicity and resistance. Recent developments include bispecific antibodies like faricimab and novel inhibitors like brorucizumab and fruquintinib. Additionally, inhibitors targeting VEGFR downstream signaling pathways, such as the RAS/RAF/MEK/ERK and PI3K/AKT/mTOR pathways, are being explored for their anti-angiogenic and anti-cancer effects. Despite progress, challenges remain in improving efficacy and reducing side effects, highlighting the need for further research and development of next-generation anti-angiogenic therapies.Recent advances in anti-angiogenic inhibitors targeting the VEGF/VEGFR axis have significantly improved the treatment of cancers and retinal diseases. VEGF and its receptors (VEGFRs) are crucial in regulating angiogenesis, both physiological and pathological. Anti-angiogenic drugs inhibit VEGF/VEGFR interactions, VEGFR tyrosine kinase (TK) activity, or downstream signaling pathways to prevent new blood vessel formation. These drugs include monoclonal antibodies, fusion proteins, and small molecules. Monoclonal antibodies like bevacizumab, ranibizumab, and aflibercept are effective in treating cancers and retinal diseases, while small molecules such as sorafenib, sunitinib, and cabozantinib target VEGFR TKs and downstream signaling pathways. These drugs have shown clinical benefits but also pose challenges such as toxicity and resistance. Recent developments include bispecific antibodies like faricimab and novel inhibitors like brorucizumab and fruquintinib. Additionally, inhibitors targeting VEGFR downstream signaling pathways, such as the RAS/RAF/MEK/ERK and PI3K/AKT/mTOR pathways, are being explored for their anti-angiogenic and anti-cancer effects. Despite progress, challenges remain in improving efficacy and reducing side effects, highlighting the need for further research and development of next-generation anti-angiogenic therapies.