Informal caregiving is crucial to the sustainability of health and social care systems globally. With ageing populations and a rising prevalence of acute and chronic health conditions, the need for informal care is growing, making it important to understand what motivates individuals to care and to continue caring. This paper reports findings of a systematic review which examined determinants of motivations and willingness to provide informal care. A systematic search was conducted using six electronic databases and a wide range of additional sources. 105 qualitative studies published before August 2019 were included with 103 of them reporting on personal and relational motivations, and the contextual factors underpinning these. Grounded theory-based, thematic synthesis was applied to synthesise the literature. This meta-synthesis reports on findings from across the world spanning three decades, with data from over 2500 caregivers across a range of health conditions. This paper presents the relational, personal and contextual themes. It highlights the significance of reciprocity, affection, family values and caregiving obligations. Personal characteristics, finding meaning, illness perceptions, situational and temporal aspects of caregiving are also identified as important in shaping motivations and willingness to care and to continue caring. Implications for theory, research, policy and practice are discussed.