A swift glance at ample evidence currently available about the assay clearly illustrates that the development of direct immunofluorescence (DIF), in which direct fluorescent antibodies are utilized to identify the target antigen, has been of immense importance. The immunoreactant deposits have been delineated by the DIF assay in three main locations, including throughout the epidermis, at the dermoepidermal junction (also known as the basement membrane zone) and in and/or around blood vessel walls. DIF testing can be conducted on several specimen sources, which are categorized according to feasibility of collection into invasive (e.g., skin) and non-invasive (e.g., hair). This review was intended to indicate that inspection of immunoreactant deposits via DIF is highly instrumental in diagnosing and monitoring the immunobullous and other diseases of the skin.