The diagnosis of skin diseases relies strongly on clinical inspection and the use of invasive diagnostic procedures. Routine histology requires the removal of tissue for microscopic evaluation, which is associated with pain, and risk of infection as well as scar formation. In the past 15 years a number of non-invasive diagnostic devices have been evaluated for use in clinical and investigative dermatology. A number of studies have assessed the applicability of confocal laser scanning microscopy (LSM) as an optical diagnostic device in dermatology. By correlating LSM images with established features of routine histology, it was possible to define diagnostic LSM parameters for a number of selected skin diseases. Present data supports the use of LSM as an adjunct diagnostic device for selected skin conditions in clinical as well as investigative dermatology. Since LSM examinations may repeatedly be performed, LSM is particularly suited for evaluation of dynamic, neoplastic and regenerative skin processes as well as the definition of disease extent and response to therapy.