When we talk about visualization methods in surgery, it is important to mention that the diagnosis of tumors and how we define tumor borders intraoperatively in a correct way are two main things that would not be possible to achieve without this grand variety of visualization methods we have at our disposal nowadays. In addition, histopathology also plays a very important role, and its importance cannot be neglected either. Some biopsy specimens, e.g., frozen sections, are examined by a histopathologist and lead to tumor diagnosis and the definition of its borders. Furthermore, surgical resection is a very important point when it comes to prognosis and life survival. Confocal laser endomicroscopy (CLE) is an imaging technique that provides microscopic information on the tissue in real time. CLE of disorders, such as head, neck and brain tumors, has only recently been suggested to contribute to both immediate tumor characterization and detection. It can be used as an additional tool for surgical biopsies during biopsy or surgical procedures and for inspection of resection margins during surgery. In this review, we analyze the development, implementation, advantages and disadvantages as well as the future directions of this technique in neurosurgical and otorhinolaryngological disciplines.