This literature review is devoted to the molecular mechanisms of oogenesis and depletion of the ovarian reserve. One of the factors in this process is constantly changing environment of the ovaries, both during intrauterine development and the postnatal period. Numerous mechanisms and factors affecting the internal environment of the female gonad are described, such as stem cell factor (SCF), which regulates migration of primordial germ cells and survival of early oocytes, insulin-like growth factor I (IGF-I), and leukocyte migration inhibitory factor (LMIF). The capabilities of the endocrine system, namely sex steroids, which can both replenish the number of germ cells and deplete the ovarian reserve through the expression of apoptotic markers, were shown. Apoptosis causes degeneration of most of the germ cells formed during oogenesis. The molecular mechanisms and factors involved in this process are numerous. Pathways mediated by mitochondria of germ cells and external pathways mediated by receptors of the cell surface were described. A mediator between two apoptotic pathways was established – the Bid protein (BH3-interacting domain death agonist), the activation of which triggers the apoptosis mechanism of the intrafollicular microenvironment. Some other factors were identified that mediate programmed germ cell death and result in diminished ovarian reserve: eukaryotic elongation factor 2 kinase (eEF-2 K), PUMA and NOXA genes, the absence of growth factors and members of tumor necrosis factor (TNF) family. Changes in the epigenetic modification of chromatin in the follicular and germ cells, oxidative stress, decreased DNA repair, and the involvement of the genes BRAC1, RAD51, ERCC2, and H2AX associated with this process can also affect reproductive health and the ovarian reserve. A significant role of mitochondrial dysfunction of follicular cells in depletion of the ovarian reserve is of great interest, which leads to impaired oocyte competence, deteriorates the gamete quality, and depletes the ovarian reserve. Therefore, oogenesis depends on a huge number of factors and the internal environment of the ovaries, the knowledge of which can maintain the stability of the reproductive function and preserve the quality of the ovarian reserve.