Non-obstructive azoospermia (NOA) with meiotic arrest is largely unknown in the majority of male infertility, which affecting about 0.6% of men from the general population and 10% of infertile men. NOA is a complicated disease caused by multiple factors which featured high genetic and phenotype heterogeneity. This condition is related to known genetic disorders, including chromosomal abnormality, Y-chromosome microdeletions, single-gene mutation and epigenetic modification. Currently, the diagnosis and treatment of patients with NOA was limited to routine epididymal puncture biopsy, karyotype analysis and Y-chromosome microdeletion detection in the clinical. Effective diagnosis and treatment strategies were deficiency for NOA with complicated etiology. Therefore, a more comprehensive exploration of the molecular mechanism of NOA will be helpful to clarify the genetic causes of non-obstructive azoospermia, the clinical diagnosis and treatment of male infertility. In this paper, we comprehensively reviewed the several aspect of NOA, including the genetic basis of NOA, the pathological features of NOA, the clinical diagnosis and treatment of NOA.