Three-dimensional scaffolds are widely used in the field of tissue engineering, which combines the principles and methods of the life sciences with those of engineering to provide a fundamental understanding of structure–function relationships in normal and diseased tissues, to develop materials and methods to repair damaged or diseased tissues, and to create entire tissue replacements [1]. A synthetic scaffold can serve as a stroma that creates a cellular environment designed to provide the factors that stimulate maturation of ovarian follicles, but lacks the factors found in the native stroma that inhibit follicle maturation. In the area of follicle maturation, synthetic scaffolds have been employed to maintain the appropriate size, shape, and architecture of the tissue while providing the necessary signals to direct cellular responses [2–7]. These scaffolds maintain the intimate physiological connections between the oocytes and somatic cells within the follicle, which are essential for normal development. Additionally, a three-dimensional scaffold is more durable and poses fewer concerns regarding jolting the cultures, which can be problematic in two-dimensional systems [5]. Finally, the scaffold-encased follicle can be individually manipulated, providing an extraordinary level of control. The development of scaffold materials, in combination with basic studies of follicle biology, will ultimately lead to the development of a synthetic ovarian stroma and the optimal media conditions to support follicle development and maturation in vitro, which will enable women to preserve their fertility in the face of various insults, including chemotherapy- or radiation therapy-induced infertility. In this chapter, we discuss the application of bioengineering principles to the emerging field of oncofertility. We will summarize current knowledge of and achievements in the development of in vitro systems for culture of preantral follicles. Then, we will discuss the concept of application of biomaterials on in vitro follicle development and principles of hydrogel selection and modification. Finally, we will address the transplantation of ovarian tissue as an alternative to in vitro maturation. Though the approach is early in its development, it has successfully yielded live offspring. Biomaterial scaffolds, combined with drug delivery technology, may facilitate engraftment and function of the transplanted tissue [8,9].