Wound healing is a highly complex biological process composed of three overlapping phases: inflammatory, proliferative, and remodeling. The acute inflammatory response has being an integral role in tissue healing and fundamental for the homeostasis and reestablishment. This phase depends on the interaction of cytokines, growth factors, chemokines, and chemical mediators from cells to perform regulatory events and complex interactions of the extracellular matrix, extracellular molecules, soluble mediators, various resident cells such as fibroblasts and keratinocytes, and infiltrated leukocyte subtypes that act to restore or replace the integrity of the skin. If this well-orchestrated response becomes deregulated, the wound can become chronic or progressively fibrotic, with both outcomes impairing tissue function, which can ultimately lead to organ failure and death. In this chapter, we will review the pathway in the skin healing cascade, relating the major chemical inflammatory mediators, cellular and molecular, as well as demonstrating the local and systemic factors that interfere in healing and disorders associated with tissue repair deficiency in chronic inflammations, burns and hypertrophy.