Lymphedema is a risk factor for the development of erysipelas, but conversely, lymphedema can also follow an infection. Therefore, infections are one of the research priorities of the Lymphedema Research Prioritization Partnership. A major problem is the question of the applicability of the conventional erysipelas definition to patients with preexisting lymphedema. While erysipelas is considered an uncomplicated skin infection, it is complicated by definition if occurring in lymphedema. The risk of spreading to deeper layers of skin is higher. Therefore, rapid and accurate therapeutic intervention is required. Pathogen detection by swab from the intact skin barrier is worthless. Empirical therapies without attempting pathogen detection contribute to the unclear data situation. In a Europe-wide epidemiological study, about 50% of patients were treated empirically. For germ analysis, repeated blood culture (Day 0 and Day 3), fine needle aspiration/ultrasound, and possibly skin biopsy in erysipelas with lymphedema are the gold standard. A 6-month recurrence prophylaxis with oral penicillin led to a reduction in the recurrence rate from 33% to 20% in erysipelas of the leg compared to placebo. In the special case of a recurrence of an infection by S. aureus, eradication of a possible nasal or dental reservoir should be considered. Entry points such as rhagades, dermatophyte, or onychomycosis must be cured in the context of lymphedema to prevent recurrent bacterial infections. From the perspective of the clinical lymphologist, a reduction in edema through manual lymphatic drainage under antibiotic protection, local cooling with black tea compresses, and potentially pain treatment significantly accelerate the healing of erysipelas in lymphedema. If the pain does not match the wound, immediate MRI diagnostics and surgical therapy are life-saving in case of suspected necrotizing fasciitis. The treatment of choice is the combination of extensive debridement and high-dose antibiotic therapy. Antibiotic therapy alone is not sufficient.