Smoldering multiple myeloma (SMM) is an asymptomatic plasma cell disorder characterized by the presence of ≥ 3 g/dL serum M-protein and/or 10% to 60% bone marrow plasma cell infiltration with no myeloma-defining event. The risk of progression to active multiple myeloma (MM) is not uniform, and several markers are useful for identifying patients at high risk of progression. The definition of the disease has recently been revisited and asymptomatic MMs at 80% to 90% of progression risk at 2 years are now considered to be active MM candidates for treatment. In the future, more precise biomarkers are necessary for accurate risk stratification to plan an optimized follow-up according to the risk of progression, as well as to expand the group of patients that can obtain a benefit if they receive early treatment. A phase 3, randomized trial in high-risk patients with SMM comparing early treatment versus observation has shown a significant benefit in terms of time to progression and overall survival for early intervention and confirmatory clinical trials will definitively contribute to establish the early treatment as standard of care in high-risk SMM.