Non-invasive diagnostic methods such as optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) are nowadays widely used in dermatological research and daily clinical routine. OCT and RCM have demonstrated high sensitivity and specificity in the diagnosis of actinic keratosis, basal cell carcinoma and squamous cell carcinoma, whereas RCM is also useful in distinguishing benign nevi from melanomas. Both methods can be used as an additional diagnostic tool for a wide spectrum of inflammatory and infectious skin diseases. Line-field confocal optical coherence tomography (LC-OCT) is a new device combining both cellular resolution and high penetration depth, so that not only tumor cell morphology but also tumor thickness can be evaluated in-vivo. Ongoing studies show promising results in the analysis of non melanoma skin cancer, field cancerization, and mites infestations. Further studies are needed to define standardized diagnostic criteria and fields of application.