CXC chemokines are a family of cytokines that regulate angiogenesis, the formation of new blood vessels. These chemokines have a unique ability to either promote or inhibit angiogenesis, depending on their structural features. The ELR motif (Glu-Leu-Arg) at the N-terminal of CXC chemokines determines their angiogenic activity. CXC chemokines containing the ELR motif (ELR⁺) are potent promoters of angiogenesis, while those lacking the ELR motif (ELR⁻) are potent inhibitors. This dual role of CXC chemokines in angiogenesis is critical for both physiological and pathological processes, including wound repair, tumorigenesis, and tumor metastasis. ELR⁺ CXC chemokines, such as IL-8, ENA-78, GRO-α, GRO-β, and GRO-γ, promote angiogenesis by directly inducing endothelial cell chemotactic and proliferative activity in vitro and angiogenesis in vivo. They act through the CXC chemokine receptors CXCR1 and CXCR2. In contrast, ELR⁻ CXC chemokines, such as IP-10, MIG, and I-TAC, inhibit angiogenesis by interfering with the activity of pro-angiogenic factors like VEGF and bFGF. These chemokines can also inhibit angiogenesis through mechanisms such as blocking the binding of these factors to their receptors or by forming heterodimers that impair their function. ELR⁺ CXC chemokines are involved in the progression and growth of various cancers, including melanoma, ovarian cancer, non-small-cell lung cancer (NSCLC), and prostate cancer. They promote tumor growth and metastasis by facilitating angiogenesis. Conversely, ELR⁻ CXC chemokines can inhibit angiogenesis and thus suppress tumor growth. In chronic fibroproliferative disorders such as idiopathic pulmonary fibrosis (IPF), the imbalance between ELR⁺ and ELR⁻ CXC chemokines contributes to dysregulated angiogenesis and fibrosis. The regulation of angiogenesis by CXC chemokines has important implications for the treatment of diseases involving abnormal angiogenesis, such as cancer and fibrotic disorders. Targeting CXC chemokines or their receptors could offer new therapeutic strategies for these conditions.CXC chemokines are a family of cytokines that regulate angiogenesis, the formation of new blood vessels. These chemokines have a unique ability to either promote or inhibit angiogenesis, depending on their structural features. The ELR motif (Glu-Leu-Arg) at the N-terminal of CXC chemokines determines their angiogenic activity. CXC chemokines containing the ELR motif (ELR⁺) are potent promoters of angiogenesis, while those lacking the ELR motif (ELR⁻) are potent inhibitors. This dual role of CXC chemokines in angiogenesis is critical for both physiological and pathological processes, including wound repair, tumorigenesis, and tumor metastasis. ELR⁺ CXC chemokines, such as IL-8, ENA-78, GRO-α, GRO-β, and GRO-γ, promote angiogenesis by directly inducing endothelial cell chemotactic and proliferative activity in vitro and angiogenesis in vivo. They act through the CXC chemokine receptors CXCR1 and CXCR2. In contrast, ELR⁻ CXC chemokines, such as IP-10, MIG, and I-TAC, inhibit angiogenesis by interfering with the activity of pro-angiogenic factors like VEGF and bFGF. These chemokines can also inhibit angiogenesis through mechanisms such as blocking the binding of these factors to their receptors or by forming heterodimers that impair their function. ELR⁺ CXC chemokines are involved in the progression and growth of various cancers, including melanoma, ovarian cancer, non-small-cell lung cancer (NSCLC), and prostate cancer. They promote tumor growth and metastasis by facilitating angiogenesis. Conversely, ELR⁻ CXC chemokines can inhibit angiogenesis and thus suppress tumor growth. In chronic fibroproliferative disorders such as idiopathic pulmonary fibrosis (IPF), the imbalance between ELR⁺ and ELR⁻ CXC chemokines contributes to dysregulated angiogenesis and fibrosis. The regulation of angiogenesis by CXC chemokines has important implications for the treatment of diseases involving abnormal angiogenesis, such as cancer and fibrotic disorders. Targeting CXC chemokines or their receptors could offer new therapeutic strategies for these conditions.