Bone is a dynamic tissue that can always rebuild itself by modeling and remodeling to maintain functionality. This tissue is responsible for several vital functions in the body, such as providing structural support for soft tissues and the body, being the central region of hematopoiesis in human adults, and contributing to mineral homeostasis. Besides, it has an innate ability of auto-regeneration when damaged. All of these processes involve several molecular cues related to biochemical and mechanical stimulus. However, when the lesion is complicated or too big, it is necessary to intervene surgically, which may not effectively solve the problem. Bone tissue engineering seeks to provide resources to resolve these clinical issues and has been advancing in recent years, presenting promising devices for bone tissue repair. The understanding of some important biofactors and bone stem-cells influence might be crucial for an effective regenerative medicine, since bone is one of the most transplanted tissues. So, the purpose of this article is to provide an overview of the bone tissue, including the role of stem cells and some of the bioactive molecules associated with these processes. Finally, we will suggest future directions for bone tissue engineering area that might be helpful in order to produce biomimetic bone substitutes that become a real alternative to translational medicine.