Significant improvements in induction therapy for multiple myeloma have been seen over the past decade for both transplant-eligible patients and transplant-ineligible patients. The emergence of novel agents in managing myeloma has revealed new directions for clinicians to approach the disease. The first determinant is transplant eligibility. With the recognition of the prognostic impact of postinduction response on overall outcomes, the importance of the choice of optimal regimen has become more important than ever. The preference of induction therapy for transplant-eligible patients has progressively changed from the alkylator-based therapies to doublet therapies to triplet therapies incorporating immunomodulatory drugs (IMiDs) and proteasome inhibitors. The role of quadruplet therapies remains unclear, but with appropriate dosage modifications, these regimens were efficacious and had an acceptable toxicity profile. Similar treatment approaches for transplant-ineligible patients resulted in superior outcomes with the triplet therapies. Many challenges remain however, such as achieving greater depth of responses with molecular remissions and more effective use of risk stratification in induction therapy. These are still to be explored.