Introduction The extracellular matrix (ECM) plays an integral role in wound healing. It provides both structure and growth factors that allow for the organised cell proliferation. Large or complex tissue defects may compromise host ECM, creating an environment that is unfavourable for the recovery of anatomical function and appearance. Acellular dermal matrices (ADMs) have been developed from a variety of sources, including human (HADM), porcine (PADM) and bovine (BADM), with multiple different processing protocols. The objective of this report is to provide an overview of current literature assessing the clinical utility of ADMs across a broad spectrum of applications. Methods PubMed, MEDLINE, EMBASE, Scopus, Cochrane and Web of Science were searched using keywords ‘acellular dermal matrix’, ‘acellular dermal matrices’ and brand names for commercially available ADMs. Our search was limited to English language articles published from 1999 to 2020 and focused on clinical data. Results A total of 2443 records underwent screening. After removing non-clinical studies and correspondence, 222 were assessed for eligibility. Of these, 170 were included in our synthesis of the literature. While the earliest ADMs were used in severe burn injuries, usage has expanded to a number of surgical subspecialties and procedures, including orthopaedic surgery (e.g. tendon and ligament reconstructions), otolaryngology, oral surgery (e.g. treating gingival recession), abdominal wall surgery (e.g. hernia repair), plastic surgery (e.g. breast reconstruction and penile augmentation), and chronic wounds (e.g. diabetic ulcers). Conclusion Our understanding of ADM’s clinical utility continues to evolve. More research is needed to determine which ADM has the best outcomes for each clinical scenario. Lay Summary Large or complex wounds present unique reconstructive and healing challenges. In normal healing, the extracellular matrix (ECM) provides both structural and growth factors that allow tissue to regenerate in an organised fashion to close the wound. In difficult or large soft-tissue defects, however, the ECM is often compromised. Acellular dermal matrix (ADM) products have been developed to mimic the benefits of host ECM, allowing for improved outcomes in a variety of clinical scenarios. This review summarises the current clinical evidence regarding commercially available ADMs in a wide variety of clinical contexts.