As a distinctive feature of traditional Chinese medicine, the combined use of acupuncture and medication has demonstrated unique advantages in the prevention and treatment of major diseases in recent years. Its value is reflected not only in the efficacy level, but also in providing multi-dimensional and multi-level intervention ideas for the research on complex pathogenesis. The combination of acupuncture and medication has undergone an evolution from experience accumulation to the standardized summarization, and then to mechanistic exploration. Modern studies have revealed that the synergy of acupuncture and medication can be interpreted from three perspectives: action level, temporal characteristics and spatial coupling. It embodies a synergistic mechanism that combines central regulation with peripheral intervention, complements immediate effect with sustained and prolonged release, and integrates multi-pathway signals. In recent years, with the development of neuroimaging, single-cell omics and multi-omics integration, the mechanism of combined acupuncture and medication will be decoded more accurately. The clinical transformation of the therapeutic strategy of combined acupuncture and medication in the field of major diseases will provide a new paradigm for comprehensive prevention and treatment under the integration of multiple disciplines.