Direct immunofluorescence (DIF) and indirect immunofluorescence (IIF) tests on skin biopsy are being done mostly in academic teaching hospitals. These tests provide a useful diagnostic aid to dermatologists. Immunohistology and serology can, in conjunction with histology, provide considerable help in delineation and diagnosis of various skin disorders as well as systemic diseases with skin involvement, e.g. systemic lupus erythematosus. Immunofluorescence (IF) studies have now become an invaluable supplement to clinical and histological examination in a variety of dermatological diseases. These skin diseases now include not only bullous and connective tissue disorders, vasculitides, and conditions such as lichen planus, but also the scaling dermatoses, notably psoriasis. In this review article, we share our experience of providing such a diagnostic facility for more than 30 years in a large tertiary care health center in North India and also help to outline the conditions, which can be diagnosed confidently, and others where IF can help in confirming a diagnosis or the immune component of the disease. The article also deals with handling of skin biopsy specimens and interpretation of biopsy findings on DIF and IIF examination.