Multiple myeloma (MM) is a plasma cell neoplasm that accounts for 2% of all haematological malignancies and predominantly affects older individuals (with a median age at diagnosis of 65-70 years). MM is consistently preceded by the clinically recognized precancerous stages monoclonal gammopathy of undetermined significance and smouldering MM. Thus far, MM has been considered as a single disease entity, but the clinical presentation, response to treatment, and survival outcomes of patients with MM are quite heterogeneous and highly dependent on a set of chromosomal abnormalities that can be identified in nearly all of them. These alterations include primary cytogenetic abnormalities, such as translocations involving chromosome 14q and trisomies of odd-numbered chromosomes, as well as secondary abnormalities, such as deletion of chromosome 17p and amplification of chromosome 1q. The aetiology of myeloma is poorly understood, although different nonoverlapping disease entities can be defined on the basis of their specific primary cytogenetic abnormalities, which have a major role in determining clinical behaviour. This classification might enable the development of better treatment strategies focused on the underlying biology of each specific subtype. Herein, we describe treatment approaches that incorporate the current standard of care for patients with MM along with recommended alterations or improvements that might provide additional clinical benefit for certain subgroups of patients.