Raman spectroscopy has shown very promising results in medical diagnostics by providing label-free and highly specific molecular information of pathological tissue ex vivo and in vivo. Nevertheless, the high specificity of Raman spectroscopy comes at a price, i.e., low acquisition rate, no direct access to depth information, and limited sampling areas. However, a similar case regarding advantages and disadvantages can also be made for other highly regarded optical modalities, such as optical coherence tomography, autofluorescence imaging and fluorescence spectroscopy, fluorescence lifetime microscopy, second-harmonic generation, and others. While in these modalities the acquisition speed is significantly higher, they have no or only limited molecular specificity and are only sensitive to a small group of molecules. It can be safely stated that a single modality provides only a limited view on a specific aspect of a biological specimen and cannot assess the entire complexity of a sample. To solve this issue, multimodal optical systems, which combine different optical modalities tailored to a particular need, become more and more common in translational research and will be indispensable diagnostic tools in clinical pathology in the near future. These systems can assess different and partially complementary aspects of a sample and provide a distinct set of independent biomarkers. Here, we want to give an overview on the development of multimodal systems that use RS in combination with other optical modalities to improve the diagnostic performance.