The majority of scalp and cranium defects usually result from traumatic injury, benign/malignant skull tumor resection, or bone flap infections. The occurrence of large scalp and cranium defects not only results in a lack of protective barriers for intracranial contents and impairment of normal brain function, but also leads to cosmetic problems. The present chapter will mainly focus on plastic surgical concepts and techniques adopted for regeneration of major scalp and cranium defects.