There is a clear scientific rationale for using cellular, acellular and matrix-like products (CAMPs), such as small intestinal submucosa extracellular matrix (SIS-ECM), in hard-to-heal wounds, such as diabetic foot ulcers (DFUs), venous leg ulcers (VLUs), pressure ulcers and arterial leg ulcers. The clinical evidence supporting the use of SIS-ECM has grown over the past several decades. This evidence base now encompasses a wide range of hard-to-heal wound indications, including DFUs and VLUs, as well as increasingly complex acute wound indications, such as delayed postoperative wounds, traumatic wounds and burns. The aim of this article is to review the steadily amassed body of evidence that describes the clinical outcomes associated with treatment with SIS-ECM and its potential implications for the overall costs of treatment.