Wound bed preparation is the promotion of wound closure through diagnosis of the cause, attention to patient-centered concerns, and correction of systemic and local factors that may delay healing. To enhance the evidence base that may be lacking, a review of relevant literature was conducted and combined with input from the International Wound Bed Preparation Advisory Board and the Canadian Chronic Wound Advisory Board to create an updated examination of practices. A template based on expert opinion of the clinical actions corresponding to each step in the paradigm of preparing the wound bed is presented and the effects of local factors (tissue debridement, infection or inflammation, moisture balance, and edge effect [TIME]) are discussed. This review differentiates increased bacterial burden/infection in the superficial and deep wound bed compartments from inflammation and provides a topical approach to treatment. Inflammatory conditions causing leg ulcers, including pyoderma gangrenosum and vasculitis are reviewed. The topical combination of silver with absorptive dressings has led to new therapeutic options for increased bacterial burden in the surface wound compartment. A compilation of the available systematic reviews for the treatment of infection has been included as a background for the expert opinion.