Objective: Multiple Myeloma (MM) is increasing in incidence and for the elderly, survival remains poor, mainly due to poor tolerance to chemotherapy which forms an important component of first-line treatment for MM. No previous study has been found on dexamethasone monotherapy for MM treatment. Case Presentation: A 75-year-old female of Chinese descent, previously independent with a background of well-controlled hypertension, type 2 diabetes, hyperlipidemia, and mild Alzheimer’s dementia presented to the general practice with fatigue, left groin pain, decreased appetite and dizziness. She was diagnosed with end-stage MM based on serum protein electrophoresis and skeletal survey and treated with only dexamethasone as a chemotherapeutic agent. Results: As of February 2022, two years after the diagnosis of end-stage MM and treatment with dexamethasone monotherapy and supportive therapy, the patient remains adherent to her management plan. She remained alive with mild functional decline and preserved renal function. Conclusions: In addition to managing patients according to the best principles of supportive care, dexamethasone monotherapy may be a good alternative maintenance agent in frail, elderly patients with MM who may not even tolerate attenuated chemotherapy.