Multiple myeloma (MM), a neoplasm of plasma cells, is the second most common hematologic malignancy. With treatment advances, patients are living longer. However, the disease remains incurable. MM patients are started on a combination of antineoplastic agents with the aim of achieving disease remission. However, at some point patients will experience a relapse requiring another type of therapy. The attrition rate is high, and the periods of remission with each line of therapy become shorter as MM becomes biologically more complex and refractory to treatment. In other words, the initial induction strategy could have a significant impact on the patient's disease trajectory because this will likely be the best and most durable response for the patient. The upfront regimen for a new MM patient is determined based on disease-specific factors such as biology (cytogenetics, circulating plasma cells, extramedullary disease) as well as patient-related factors such as performance status, organ impairment, comorbidities, and fitness status. For patients considered fit, the treatment goal is to achieve maximum therapeutic efficacy to obtain the best disease response. The definition of fitness varies for each trial, and it is a subjective assessment by the provider. It does not necessarily correlate with whether a patient is considered transplant eligible. Patients may choose to defer transplant or may not be offered a transplant based on age cutoff geographically despite being fit. These patients are included in studies for transplant-ineligible patients. In this review, we evaluate the best induction regimen for MM patients fit for treatment.