Topical wound therapies have unclear benefits for patients with pressure ulcers, venous leg ulcers (VLUs), and arterial ulcers. There is slightly more evidence supporting the use of systemic therapies. Used with compression therapy or alone, oral pentoxifylline has been shown to be more effective than placebo or no therapy in improving and healing VLUs. (This is an off-label use of pentoxifylline.) To prevent bacterial resistance, most guidelines recommend use of antimicrobial dressings, antiseptics, and antibiotics only for patients with infected wounds. There is insufficient evidence to conclude that antiseptics or topical antibiotics improve or heal pressure ulcers and VLUs more effectively than nonmedicated dressings. Systemic antibiotics are used for patients with nonhealing wounds when the clinical infection is not improving with antiseptics or topical antibiotics. After the underlying cause of a chronic wound is addressed, pain management should start with topical drugs. When pain is not managed with topical drugs, systemic drugs should be considered. Opioids should be used only if the overall benefits outweigh the risks. Nutritional supplementation has not been clearly shown to prevent or manage chronic ulcers.