Electrospinning has been employed extensively in tissue engineering to generate nanofibrous scaffolds from either natural or synthetic biodegradable polymers. Three-dimensional electrospun scaffolds can create a multi-scale environment capable of facilitating cell adhesion, proliferation, and differentiation. One such multi-scale scaffold incorporates nanofibrous features to mimic the extracellular matrix along with a porous network for the regeneration of a variety of tissues. This review will discuss nanofibrous scaffolds and their tissue-engineering applications in bone, cartilage, periodontium, tooth, and incorporated drug delivery systems. Combination with other technologies, electrospun scaffolds can contribute to the field of craniofacial regeneration and advance technology for tissue-engineered replacements in many physiological systems in near future.