Caveolae are specialized flask-shaped lipid rafts enriched in cholesterol, sphingolipids, and structural marker proteins termed caveolins. Caveolins are highly conserved hairpin loop-shaped, oligomeric proteins of 22-24 kDa. Besides the plasma cell membrane, caveolins are also present in mitochondria, the endoplasmatic reticulum, the Golgi/trans-Golgi network, and secretory vesicles. They play a critical role in normal vesicular transport, cholesterol homeostasis, and signal transduction. Conversely, dysregulation of caveolin-1 has been associated with several human diseases including multiple myeloma, an incurable malignancy characterized by excess monoclonal plasma cells within the bone marrow. In this mini-review, we characterize the functional role of caveolin-1 in multiple myeloma, and present the preclinical rationale for novel potential therapeutic approaches targeting caveolin-1 in multiple myeloma.