In this review, we will discuss the self-regulation and regulation of netrin-1 in the disease microenvironment from three perspectives: acute inflammatory diseases (ischemic stroke, acute lung injury, and acute kidney injury), chronic inflammatory diseases (diabetes, atherosclerosis, abdominal aortic aneurysm, osteoarthritis, pulmonary fibrosis, and endometritis), and cancer (glioblastoma and non-small cell lung cancer). This evidence concerns the gene NTN1 and non-small cell lung carcinoma.