The primary motivating factor for blood donation is altruism and its derivatives, such as empathy and social responsibility. However, no conclusive answers were obtained from the analysis of these articles, indicating the need for further studies focused on this topic. In Brazil, blood donation is voluntary, unpaid, and anonymous. Despite being a reference in Latin America for improving voluntary donation rates and expanding the age range of potential donors, there are still many challenges related to this practice, as only 1.9% of the Brazilian population are blood donors. This article aims to identify, through a literature review, the main motivations for blood donation. For this purpose, a systematic review was conducted, including studies published in English, Portuguese, and Spanish between 2013 and 2023, from the PubMed, SciELO, and LILACS databases, using MeSH queries with the descriptors “blood donors,” “donor motivation,” and “motivation.” Original articles and review articles were included. A total of 207 articles were identified in February and March 2023, and after applying the inclusion criteria, 25 articles were selected for the study. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO-CRD42023431808) and concluded that the main motivator for blood donation was altruism and its “derivatives,” such as empathy and social responsibility. No conclusive answers were obtained from the analysis of these articles, which necessitates further studies on this topic.