Primary ovarian insufficiency (POI) is characterized by loss of ovarian function before the age of 40 years. It is one of the most important causes of female infertility. POI is a heterogeneous condition; it can be associated with additional congenital or acquired abnormalities. A wide range of etiological factors may cause POI including genetic, metabolic, autoimmune, infectious and toxic. The genetic basis of this condition can be related to chromosomal, monogenic and multifactorial genetic disorders. Recently, many new genes causing POI have been identified using next generation sequencing-based technologies. I will review genetic causes of syndromic and non-syndromic forms of POI including two new genes identified by our group, SYCE1 and SPIDR. Both of these genes cause autosomal recessive non-syndromic POI. The SYCE1 gene encodes a component of the synaptonemal complex; the protein encoded by the SPIDR gene might be important in homologous recombination. The identification of causative mutation would provide better opportunity for early intervention. Most importantly, identification of specific gene defects and biological pathways will help to identify potential targets for future treatment.