A key structural protein in the extracellular matrix, collagen is essential for preserving the integrity and functionality of tissues. This chapter explores its genesis, classification, hierarchical structure, and biomedical importance. Collagen-based biomaterials (CBBs) have transformed various therapeutic applications, including drug delivery systems, orthopedic implants, and wound healing. The study also briefly describes some autoimmune and hereditary conditions, including Systemic sclerosis, Ehlers-Danlos syndrome, Alport syndrome, etc., connected to collagen disorders. Collagen-based therapeutics continue to face obstacles despite their vast biological inventions. Modern fabrication methods and biomaterial engineering advancements are crucial for maximizing collagen’s clinical applications in regenerative medicine and diagnostics.