Background E-learning is recognised as a useful educational tool and is becoming more common in undergraduate medical education. This review aims to examine the scope and impact of e-learning interventions on medical student learning in clinical medicine, in order to aid medical educators when implementing e-learning strategies in programme curricula. Methods A systematic review compliant with PRISMA guidelines that appraises study design, setting and population, context and type of evaluations. Specific search terms were used to locate articles across nine databases: MEDLINE/PubMed, ScienceDirect, EMBASE, Cochrane Library, ERIC, Academic Search Complete, CINAHL, Scopus and Google Scholar. Only studies evaluating e-learning interventions in undergraduate clinical medical education between January 1990 and August 2021 were selected. Of the 4,829 papers identified by the search, 42 studies met the inclusion criteria. Results The 42 studies included varied in scope, cognitive domain, subject matter, design, quality and evaluation. The most popular approaches involved multimedia platforms (33%) and case-based approaches (26%), were interactive (83%), asynchronous (71%) and accessible from home (83%). Twelve studies (29%) evaluated usability, all of which reported positive feedback. Competence in use of technology, high motivation and an open attitude were key characteristics of successful students and preceptors. Conclusions Medical education is evolving consistently to accommodate rapid changes in therapies and procedures. In today's technologically adept world, e-learning is an effective and convenient pedagogical approach for the teaching of undergraduate clinical medicine.