The impact upon health-related quality of life (HRQoL) in the neuropathic pain patients is greater than the sufferers of chronic conditions such as heart failure, cancer, chronic obstructive pulmonary disease, and motor neuron disease. This chapter focuses on the HRQoL in different neuropathic pain conditions and looks at the domains with high scores as assessed by the patient and recommended by Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT). Chronic pain significantly affects physical functioning, however not every individual is disabled by pain, neither is there consistency in increasing disability with increasing pain. Positive coping responses such as task persistence, distraction, and positive self talk, result in better functional outcomes and lower pain intensity. An important clinical implication of the relationship between pain and catastrophizing lies in understanding that there are factors other than tissue damage or nociception which may contribute to higher ratings of pain intensity.