Background: Short-term medical missions (STMMs) represent a grass-roots form of aid, transferring medical services rather than funds or equipment. The objective of this paper is to review empirical studies on social, economic and diplomatic aspects of STMMs. Methods: A systematic literature review was conducted by searching PubMed and EBSCOhost for articles published from 1947-2014 about medical missions to lower and middle income countries (LMICs). Publications focused on military, disaster and dental service trips were excluded. A data extraction process was used to identify publications relevant to our objective stated above. Results: PubMed and EBSCOhost searches provided 4138 and 3262 articles respectively for review. Most articles that provide useful information have appeared in the current millennium and are found in focused surgical journals. Little attention is paid to aspects of volunteerism, altruism and philanthropy related to STMM activity in the literature reviewed (1 article). Evidence of professionalization remains scarce, although elements including guidelines and tactical instructions have been emerging (27 articles). Information on costs (10 articles) and commentary on the relevance of market forces (1 article) are limited. Analyses of spill-over effects, i.e., changing attitudes of physicians or their communities towards aid, and characterizations of STMMs as meaningful foreign aid or strategic diplomacy are few (4 articles). Conclusions: The literature on key social, economic and diplomatic aspects of STMMs and their consequences is sparse. Guidelines, tactical instructions and attempts at outcome measures are emerging that may better professionalize the otherwise unregulated activity. A broader discussion of these key aspects may lead to improved accountability and intercultural professionalism to accompany medical professionalism in STMM activity.