The accurate diagnosis of bullous and other immune diseases of the skin requires evaluation of clinical, histologic, and immunofluorescence findings. Immunofluorescence testing is invaluable in confirming a diagnosis that is suspected by clinical or histologic examination. This is especially true in subepidermal bullous diseases that often have overlap in the clinical and histologic findings. Direct immunofluorescence is performed on perilesional skin for patients with bullous diseases and lesional skin for patients with connective tissue diseases and vasculitis. (J Am Acad Dermatol 2001;45:803-22.) Learning objective: At the completion of this learning activity, participants should be familiar with the ideal method of obtaining immunofluorescence testing for the diagnosis of immune skin diseases and be aware of the value and limitations of immunofluorescence studies.