Our knowledge of myeloma genetics remained limited and lagged behind many other hematologic malignancies because of the inherent difficulties in generating metaphases within the malignant plasma cell clone. With the development of molecular techniques (microarrays and next-generation sequencing), our understanding has been highly improved in the past 5 years. These studies have not only confirmed the prevalence of wide heterogeneity in myeloma at the molecular level, but has also provided a much clearer picture of the disease pathogenesis and progression. Whether these data will enable improvements in the therapeutic approach is still a matter of debate. The next improvement will come from detailed analyses of these molecular features to try to move from a treatment fitted to every patient to individualized therapies, taking into account the complexity of the chromosomal changes, the mutation spectrum, and subclonality evolution.