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Multiple myeloma (MM) is a hematological disease characterized by the uncontrolled proliferation of bone marrow malignant plasma cells. Localization and survival of malignant cells relies on bone marrow niche, in turn determined by the interaction between MM cells and mesenchymal stromal cells (MSCs). Several reports suggest that Hedgehog (Hh) pathway plays an outstanding role in tumor microenvironment maintenance. Hh signaling or-150 Vol. 2(2), 149-159, 2022 IMPACT STATEMENTSeveral reports investigated the role of Hedgehog signaling in multiple myeloma progression. In this review we discuss the recent advancements in this field, also considering the new drugs currently in clinical trial.