Major neuro-cognitive disorders are life-limiting illnesses. However, unlike other life-limiting illnesses, the disease trajectory is often long, protracted and unpredictable. Prognostication of end of life can be problematic and access to specialist palliative care services, including hospice, are limited, variable and inequitable, resulting in negative experiences at this time. Major neuro-cognitive disorders will be discussed initially in broad terms, considering the most common types and symptoms. Palliative and end-of-life care, including legal and ethical issues, are addressed and awareness raised of different types of major neuro-cognitive disorders, common symptoms and common nursing problems associated with major neuro-cognitive disorders at end of life. The needs of family and lay caregivers, who form an important part of the overall experience of major neuro-cognitive disorders, are also highlighted. Advance Care Planning is an important part of end-of-life care. Some of the challenges involved in facilitating Advanced Care Planning (ACP) with people with major neuro-cognitive disorders and caregivers are also considered. The need for palliative care practitioners to recognise the individuality of the patient and be aware that not all patients experiencing major neuro-cognitive disorders share the same set of symptoms, as in other life limiting illnesses, is also highlighted. It is important for specialist palliative care practitioners to recognise the transferability of existing knowledge, skills and expertise to the care of people with advanced major neuro-cognitive disorders as end of life approaches. Collaboration, partnership and the sharing of knowledge and skills is crucial to the development of good end-of-life care for people with these conditions, development of the workforce and the creation of positive experiences and subsequent memories after death.