Background: Recently, much attention has been given to e-learning in higher education as it provides better access to learning resources online, utilising technologyregardless of learners' geographical locations and timescaleto enhance learning. It has now become part of the mainstream in education in the health sciences, including medical, dental, public health, nursing, and other allied health professionals. Despite growing evidence claiming that e-learning is as effective as traditional means of learning, there is very limited evidence available about what works, and when and how e-learning enhances teaching and learning. This systematic review aimed to identify and synthesise the factorsenablers and barriersaffecting e-learning in health sciences education (el-HSE) that have been reported in the medical literature. Methods: A systemic review of articles published on e-learning in health sciences education (el-HSE) was performed in MEDLINE, EMBASE, Allied & Complementary Medicine, DH-DATA, PsycINFO, CINAHL, and Global Health, from 1980 through 2019, using 'Textword' and 'Thesaurus' search terms. All original articles fulfilling the following criteria were included: (1) e-learning was implemented in health sciences education, and (2) the investigation of the factorsenablers and barriersabout el-HSE related to learning performance or outcomes. Following the PRISMA guidelines, both relevant published and unpublished papers were searched. Data were extracted and quality appraised using QualSyst tools, and synthesised performing thematic analysis. Results: Out of 985 records identified, a total of 162 citations were screened, of which 57 were found to be of relevance to this study. The primary evidence base comprises 24 papers, with two broad categories identified, enablers and barriers, under eight separate themes: facilitate learning; learning in practice; systematic approach to learning; integration of e-learning into curricula; poor motivation and expectation; resource-intensive; not suitable for all disciplines or contents, and lack of IT skills. Conclusions: This study has identified the factors which impact on e-learning: interaction and collaboration between learners and facilitators; considering learners' motivation and expectations; utilising user-friendly technology; and putting learners at the centre of pedagogy. There is significant scope for better understanding of the issues related to enablers and facilitators associated with e-learning, and developing appropriate policies and initiatives to establish when, how and where they fit best, creating a broader framework for making e-learning effective.