In the past, most patients with multiple myeloma (MM) died within 5 to 10 years after diagnosis. Within the past decade, several new therapeutic interventions have been introduced, including autologous stem-cell transplantation, thalidomide, lenalidomide, and bortezomib. We estimated trends in age-specific 5- and 10-year relative survival of patients with MM in the United States from 1990-1992 to 2002-2004 from the 1973-2004 database of the Surveillance, Epidemiology, and End Results (SEER) Program. Techniques of period analysis were used to show most recent developments. Overall, 5-year relative survival increased from 28.8% to 34.7% (P < .001), and 10-year relative survival increased from 11.1% to 17.4% (P < .001) between 1990-1992 and 2002-2004. Much stronger increases were seen in the age group younger than 50 years, leading to 5- and 10-year relative survival of 56.7% and 41.3% in 2002-2004, and in the age group 50 to 59 years, leading to 5- and 10-year relative survival of 48.2% and 28.6% in 200-2004. By contrast, only moderate improvement was seen in the age group 60 to 69 years, and essentially no improvement was achieved among older patients. Our period analysis discloses a major increase in long-term survival of younger patients with MM in recent years, which most likely reflects the effect of recent advances in therapy and their dissemination in clinical practice.