Skin substitutes have emerged as a critical component in the management of complex wounds, burns, and chronic ulcers. These biomaterials are designed to replicate the structural, functional, and physiological properties of the native skin and promote effective wound healing and tissue regeneration. Skin substitutes are generally divided into two main categories based on their source: biological and polymeric skin substitutes. Biological substitutes, sourced from human or animal tissues, closely resemble the natural extracellular matrix and are often favored for their biocompatibility. On the other hand, polymer-based substitutes offer advantages such as tunable properties, and ease of fabrication. This chapter provides a comprehensive overview of both types of skin substitutes, highlighting their clinical applications, strengths, and limitations. Furthermore, current research trends and innovations in the field are explored. The chapter also delves into the fabrication methods used in developing skin substitutes, discussing the advantages and challenges associated with each technique to give a holistic view of the field.