Chronic kidney disease (CKD) is a progressive disease that demands considerable time investment for proper management including diet and lifestyle modification, managing numerous medications, and attending medical appointments. Complex and highly variable pharmacology, frequent monitoring and evaluation to maintain optimal pharmacotherapy, clinic and drug adherence, and treatment of comorbidities and other risk factors are all part of the medical management of both pre-dialysis and dialysis patients. Patients with CKD and their families bear heavy suffering and financial burdens because of the disease’s intricate course and complicated treatment. Therefore, patients’ health-related quality of life (HRQoL) is negatively impacted by CKD. Poor HRQoL has been a significant problem for patients with CKD, and it can have a detrimental effect on how the disease progresses. Poor HRQoL has been a major issue across the spectrum of patients at different stages of CKD. This chapter highlights the risk factors, etiology, global epidemiology, staging, signs, and symptoms of CKD, CKD as a public health problem, and HRQoL of patients at various stages of pre-dialysis CKD, significant determinants of poor HRQoL in pre-dialysis CKD, and interventions needed to improve HRQoL in pre-dialysis CKD.