Abstract: After a development period of approximately 20 years, anti-angiogenic therapy has now become an important therapeutic tool for neoplasms as it has been shown to have efficacy in combination with chemotherapy, radiotherapy, epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy, and even immunotherapy. However, specific effects of antiangiogenic drugs on the tumor microenvironment lead to specific "bottlenecks" of antiangiogenic therapy. These include the following: how to effectively overcome drug-resistance, how to predict efficacy at an early stage, how to identify the optimal population, and how to diminish toxicity. To fully take advantage of antiangiogenic drugs and to promote their use, these questions need to be answered.