In recent decades, multiple myeloma (ММ) has no longer been regarded as an incurable orphan malignancy, but has been rather considered to be a chronic disease with substantially improving options of treatment based on the new classes of chemotherapy drugs. Insight into biology of MM as well as the development and introduction of new drugs into clinical practice considerably improved survival rates. Risk stratification of MM patients on the basis of cytogenetic and molecular genetic analyses is now regarded as a key approach to the optimal treatment decision making. High-risk and aggressive MM patients are predominantly treated with combined chemotherapy protocols with 3–5 drugs including new effective agents of different classes (proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, etc.). Apart from the risk assessment, an important tool for clinical decision making is minimal residual disease (MRD) monitoring. Achieving MRD-negativity is associated with better survival rates which allow further development of response-adapted treatment strategies. Perspectives for the precision (personalized) MM treatment are still limited due to the extreme heterogeneity of molecular genetic landscape of the tumor. Further studies are necessary to prove the efficacy of this approach. Thus, the current MM therapy is based on the assessment of risk parameters using the results of standard cytogenetic and molecular genetic analyses, MRD monitoring, and personalized approach, all of which provide a considerable improvement of both immediate and long-term outcomes of MM treatment.