Application of modern and innovative spectroscopic and microscopic approaches to biomedical analysis opens new horizons and sheds new light on many unexplored scientific territories. In this review, we critically summarize up-to-date Raman-based methodologies for red blood cells (RBCs) analysis used in biology and medicine, and compare them with both classical, as well as other spectroscopic and microscopic approaches. The main emphasis is put on advantages, disadvantages and capabilities of each technique for detection of RBC deteriorations and RBC-related diseases. Although currently used classical techniques of medical analytsis serve as a gold standard for clinicians in diagnosis of erythropathies, they provide insufficient insight into RBC alterations at the molecular level. In addition, there is a demand for non-destructive and label-free analytical techniques for rapid detection and diagnosis of erythropathies. Their recognition often requires multimodal methodology comprising application of methods including sophisticated spectroscopy-based techniques, where Raman-based approaches play an important role.