Inappropriate prescription has been associated with mounting rates of antibiotic resistance worldwide, demanding more detailed studies into physicians' decision-making process. Accordingly, this study sought to explore physicians' perceptions of factors influencing antibiotic prescribing. A systematic search was performed for qualitative studies focused on understanding physicians' perceptions of the factors, attitudes and knowledge influencing antibiotic prescription. Of the total of 35 papers selected for review purposes, 18 solely included physicians and the remaining 17 also included patients and/or other healthcare providers. Data collection was based mainly on interviews, followed by questionnaires and focus groups, and the methodologies mainly used for data analysis were grounded theory and thematic analysis. Factors cited by physicians as having an impact on antibiotic prescribing were grouped into those that were intrinsic (group 1) and those that were extrinsic (group 2) to the healthcare professional. Among the former, physicians' attitudes, such as complacency or fear, were rated as being most influential on antibiotic prescribing, whilst patient-related factors (e.g. signs and symptoms) or healthcare system-related factors (e.g. time pressure and policies/guidelines implemented) were the most commonly reported extrinsic factors. These findings revealed that: (i) antibiotic prescribing is a complex process influenced by factors affecting all the actors involved, including physicians, other healthcare providers, healthcare system, patients and the general public; and (ii) such factors are mutually dependent. Hence, by shedding new light on the process, these findings will hopefully contribute to generating new and more effective strategies for improving antibiotic prescribing and allaying global concern about antibiotic resistance. Copyright © 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.