We have done a systematic review of all randomised studies in myeloma, identified through a comprehensive search. Our aim was to investigate and critically examine the effects of various treatment modalities on outcome in patients with multiple myeloma and address 22 specific clinical questions in the management of this disease. As a result of our analysis we identified two therapeutic advances in the management of myeloma that, according to the evidence, are most important for improving outcome. These advances were: introduction of high dose chemotherapy, which appears to be superior to conventional chemotherapy, and the use of bisphosphonates, which decrease the probability of pathological vertebral fractures. However, the overall quality of the body of evidence for myeloma management was poor. Many trials were done with small sample sizes, and did not include reporting power analysis. The majority of studies had inadequate allocation concealment, and few were analysed according to intention to treat principle. We conclude that the quality of total evidence supporting treatment recommendations in myeloma is modest at best and has an ample scope for improvement.