The clinical efficacy of acupuncture-moxibustion (AM) mainly depends on acupoints, but the relationship between the acupoints and AM remains unclear. Improving clinical efficacy and clarifying the mechanisms of AM is critical. We found that the specificity and sensitivity of acupoints, the skill of operation, and reasonable amount of stimulation can significantly improve the efficacy of AM. In addition, some studies have shown that Neural-Endocrine-Immune network and metabolites are involved in this process, clarifying the therapeutic mechanism of acupoints. Therefore, how to effectively use acupoints to improve the clinical efficacy of AM is one of the key issues in need of an urgent solution. In summary, this article reviewed the Chinese and English databases on the clinical efficacy and underlying mechanisms of acupoints to clarify the relationship between acupoints and AM efficacy and ultimately improve clinical efficacy through effective and rational use of acupoints.