Background: Self-medication, practiced globally is an important public health problem. Research studies have indicated inappropriate self-medication results in adverse drug reactions, disease masking, and inaccurate diagnosis of disease, increased morbidity, drug interactions, antibiotic resistance and wastage of healthcare resources. Rationale: Several self-medication systematic reviews have been written for specific population like adolescents, elderly population and medical students, etc. or for particular country or for specific disease. As the issue of self-medication and associated antibiotic resistance presents an important global public health problem with a reported worldwide increase in self-medication practices in the last decade, an integration of available global self-medication data could be useful to get a comprehensive yet comparative understanding about associated problems, antibiotic resistance, reaching stronger conclusions and planning future intervention than those drawn from reviews on specific target diseases or populations. We therefore intended to systematically review the existing literature on global self-medication practices in order to gain comprehensive information regarding prevalence, sample populations, medications used, target disease and reasons for self-medication. Methods: We conducted a systematic review of the literature on self-medication practices by searching, PubMed Medline and Web of Science database using the following combination of keywords - self-medication, self-prescription, non-prescription. Truncation was used to ensure retrieval of all possible variations of search terms. The search was limited to articles published between 1st January 2000 and 31st December 2016, human studies and English language. Duplicate and irrelevant studies were excluded from the final review. Results: A total of 140 studies covering 189279 subjects from children, adults, to geriatric population, with the overall prevalence of SM ranging from 0.1% to 100%, were included in the review. Studies were from diverse geographical locations. Majority of the studies were from Brazil (12; 9%), followed by 9 (6%) each from India (9; 6%) and Pakistan and 8 (6%) from Nigeria. Most of the studies (44; 31%) were done to find antibiotic SM prevalence, and 75 (54%) studies were done without any specific therapy area focus. Antibiotics (82; 59%), followed by NSAID’s (43.31%), and cough and cold medicines (13.9%) were the most widely self-medicated drugs. Cough and cold (61.43%), body pain (45; 32%), gastrointestinal complaints (44. 31%) were the top reported health complaints in the studies and pharmacy (80.57%), relatives & friends (45.32%), left overs (31; 22%), were the most common sources of self-medication. Conclusion: Self-medication was seen as a widespread phenomenon along with antibiotics as most widely self- medicated drugs. The World Health Organization reported alarming levels of resistance to antibiotics in member countries. The misuse of antibiotics poses a serious risk to infectious disease control and public health in general. Lack of knowledge in lay people and lack of attention of the public health researchers regarding not only self-medication but associated important problem like antibiotic resistance and potential adverse events deserves immediate implementation public health programs for increasing awareness and importance of this issue. At the same time, while implementing the rules and regulations governments should improve on providing adequate and affordable access to health care services. Further cross sectional studies with a standardized methodological approach are needed to gain better comparative understanding of global SM prevalence and practices.