Multiple myeloma (MM) is characterized by the accumulation of monoclonal plasma cells in the bone marrow (BM). The interaction between the BM microenvironment and MM plasma cells can influence cell proliferation, drug resistance and prognosis of the disease. The BM microenvironment (BMME) consists of a cellular and non‑cellular compartment. The cellular compartment includes stromal cells, endothelial cells, osteoclasts and osteoblasts, and the non‑cellular compartment includes the extracellular matrix (ECM) and the liquid milieu, which contains cytokines, growth factors and chemokines. The complex interaction between the BM microenvironment and MM plasma cells influences disease development and prognosis. The present review focuses on the interaction between malignant plasma cells and the BM microenvironment during MM progression. An improved understanding of the interaction between MM plasma cells and their microenvironment will enable the development of novel therapeutic tools that can be used in the treatment of MM, a currently incurable blood cancer.