Multiple myeloma (MM) is an incurable plasma cell (PC) malignancy characterized by the accumulation of monoclonal PCs in the bone marrow. For deeper understanding of the molecular mechanisms involved in the development of this disease, the influence of microenvironment, or the prediction of response of tumor PCs to anti-MM treatment, it is possible to use modern technologies for genomic and proteomic analyses. Due to progress in instrumentation, one of the main tools of proteomic analysis is mass spectrometry in combination with chosen separation techniques. This review will provide a short survey of the most commonly used proteomic techniques and show examples of their applications in MM proteome studies.