Background: Health-related quality of life (HRQoL) is a recognized and important outcome after stroke. An increased survival and the presence of moderate impairment in long-term stroke survivors impact their HRQoL. Methods: HRQoL measures and HRQoL determinants in stroke survivors are reviewed. Results: Stroke is the leading cause of long-term disability in western countries. Specific HRQoL scales have been developed in the last years, such as the Stroke Impact Scale, the Stroke Specific Quality of Life Scale, the Stroke and Aphasia HRQoL Scale, and the Burden of Stroke Scale. Disability and poststroke depression are consistent determinants of HRQoL. Other determinants include female sex, coping strategies, and social support. Poststroke depression affects HRQoL, functional recovery, cognitive function and healthcare use in stroke survivors. Stroke caregivers have lower HRQoL, greater prevalence of stress and depression, economical burden, and changes in social relationships. Advancing age and anxiety in patients and caregivers, high dependency and poor family support identify caregivers at risk of adverse outcomes. Conclusions: Physical and psychosocial well-being is greatly affected in stroke survivors and their caregivers.