Total pancreatectomy (TP) is a major surgical procedure that results in the complete removal of the pancreas, leading to profound metabolic and digestive challenges. Even though TP is relatively uncommon compared to the more frequently performed partial pancreatic resections, it is necessary in some forms of chronic pancreatitis, in pancreatic neoplasms and premalignant lesions with extensive involvement of the pancreatic parenchyma and in high-risk familial pancreatic cancer. Patients who undergo TP develop endocrine and exocrine pancreatic insufficiency. Type 3c or pancreatogenic diabetes is characterized by the loss of both insulin and glucagon production, making blood sugar control highly unpredictable and increasing the risk of severe hypoglycemia and diabetic ketoacidosis. Additionally, the absence of pancreatic exocrine function requires lifelong pancreatic enzyme replacement therapy for proper digestion and nutrient absorption. Chronic diarrhea, osteoporosis, and liver steatosis are some additional conditions that post-TP patients may be faced with. Beyond the physical effects, TP also affects psychological well-being, with many patients experiencing anxiety, depression, and emotional distress as they adapt to new lifestyle demands. Furthermore, when TP is undertaken for malignant disease, the above effects are compounded by the impact of the cancer diagnosis. Generally, TP is considered an inherently life-limiting operation, regardless of underlying malignancy, due to the profound physiological disruptions it causes. The complete loss of pancreatic endocrine and exocrine function often results in brittle diabetes, as well as severe malabsorption and a lifelong dependency on insulin and enzyme replacement therapy. These metabolic challenges not only increase morbidity but also significantly impact patients’ quality of life, functional capacity, and long-term survival. Even in cases of non-malignant disease, the cumulative burden of these complications makes TP a highly disabling procedure. Managing life without the pancreas demands a multidisciplinary approach to manage complications and maintain overall health. From the point of view of disability, which is not commonly considered in the literature in this context, alongside purely physical effects of the procedure, individuals living post-TP face psychological and social challenges, including dependence on medical therapies, dietary restrictions and potential impairments in daily activities. Comprehensive long-term care strategies, patient education and access to specialized support systems are crucial in optimizing their functional outcomes and overall well-being.