Most of the mammalian follicles undergo a degenerative process called “follicle atresia”. Apoptosis of granulosa cells is the main characteristic of follicle atresia. Follicle stimulating hormone (FSH) and the transforming growth factor β (TGF-β) superfamily have important regulatory functions in this process. FSH activates protein kinase A and cooperating with insulin receptor substrates, it promotes the PI3K/Akt pathway which weakens apoptosis. Both Smad or non-Smad signaling of the transforming growth factor β superfamily seem to be related to follicle atresia, and the effect of several important family members on follicle atresia is concluded in this article. FSH and TGF-β are likely to mutually influence each other and what we have already known about the possible underlying molecular mechanism is also discussed below.