Clonal evolutionary models of myeloma progression were the main focus with respect to basic science highlights at ASH 2012. The well-documented evidence for the existence of a “Darwinian-branching” evolution pattern has major clinical implications for the development of new treatment strategies and disease monitoring. As treatment results for myeloma have been further improved in most patient cohorts, an easy to use score for identification of high-risk patients with shortened overall survival (OS) has been established (elevated LDH, International Staging System (ISS) stage 3 disease, presence of cytogenetic aberrations t(4;14) and/or del 17p), while further evidence supporting the use of cereblon expression as a biomarker of IMiD (Thalidomid, Lenalidomide, Pomalidomide (POM)) response was presented. Multiple presentations delivered further positive evidence of the usefulness of maintenance and/or consolidation elements in myeloma therapies. A good example came from the Italian VMPT-VT vs. VMP trial proofing both a considerable progression free (11 months)—and OS benefit in a large phase III setting, comparing a quadruplet induction with doublet maintenance with a standard triplet induction therapy. In relapsed and refractory myeloma with both Bortezomib and IMiD pretreatment, POM and low dose Dexamethason were proved to be superior to high dose Dexamethason in a phase III trial that is expected to lead to drug registration of POM in the near future. Five presentations gave evidence for the applicability of Bendamustin based combination therapies in third and later lines of therapies, with good results even in elderly patients.