Pain is a troublesome problem in multiple myeloma (MM) patients which may be affected by several pain syndromes sustained by different underlying causes and mechanisms- In this setting may be due to the disease itself, to its complications, to diagnostic procedures and therapeutic interventions. Most pain syndromes origin from the skeleton and are related to several aspects of the myeloma bone disease (osteolysis and osteopenia). Other remarkable pains frequently observed in MM are due to disease-related and iatrogenic neuropathies. For most MM patients the World Health Organization's three-step analgesic ladder can be effective, although difficult-to-treat pain conditions are frequently observed, given the occurrence of some prognostically negative features, such as the mechanical instability and some neuropathic conditions. Therefore, the management of pain in this setting should require a multidisciplinary approach and the application of causal interventions (chemotherapy and radiotherapy) and of other pain-relieving procedural measures (i.e. vertebroplasty and orthopedic surgery). A prompt treatment of pain is necessary in order to avoid potentially devastating consequence, such the occurrence of chronic pain syndromes which may be due to central sensitization.