Oral pomalidomide (Imnovid® [EU]; Pomalyst® [USA]) in combination with dexamethasone (in the EU), is approved in several countries for the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least two prior therapies, including lenalidomide and bortezomib, and have demonstrated disease progression on the last therapy (or progression within the last 60 days in the USA). The key therapeutic mechanisms of action of pomalidomide, a thalidomide analogue, reside in its immunomodulatory, antiproliferative and anti-angiogenic effects. In the pivotal, multinational phase II MM-002 and phase III MM-003 trials, pomalidomide plus low-dose dexamethasone was effective and had a manageable safety and tolerability profile in adult patients with relapsed and refractory multiple myeloma who had received at least two prior antimyeloma therapies, including at least 2 cycles of both lenalidomide and bortezomib. Moreover, compared with high-dose dexamethasone, treatment with pomalidomide plus low-dose dexamethasone significantly prolonged progression-free survival, overall survival and time to disease progression, and improved overall response rates in the intent-to-treat population. In general, improvements in these clinical outcomes with pomalidomide plus low-dose dexamethasone treatment were also observed in subgroups of patients, including those refractory to lenalidomide, bortezomib or both drugs, those who had received several prior antimyeloma therapies, patients with renal impairment, elderly patients and those with a high-risk cytogenetic profile. Thus, combination therapy with pomalidomide plus low-dose dexamethasone is an important emerging treatment option for use as salvage therapy in patients with relapsed and refractory multiple myeloma.