Dementia is an increasing problem in Singapore’s ageing population with the most common being Alzheimer’s disease, vascular dementia, and mixed dementia. Creutzfeldt-Jakob Disease (CJD) is a fatal neurodegenerative condition that causes rapidly progressive dementia. It is a rare human transmissible prion disease with limited literature in Southeast Asia. In this article, we report 2 patients diagnosed with CJD who presented to primary care with rapidly progressive dementia, behavioral changes, and rapid functional decline. Deterioration of their clinical condition was relentless, and treatment remained palliative and supportive. It is important for family physicians to be cognisant of the clinical manifestations of CJD. We will outline the role of family physicians in the management of patients with CJD in different healthcare settings – general practice, tertiary hospital, community hospital and hospice home care.