BACKGROUND: Antimicrobial resistance (AMR) has risen high on the global health agenda in recent years. Governments around the world have been required to develop plans to address AMR, including antibiotic stewardship programmes. With antibiotic use increasing globally, and increasing awareness of the multiple arenas in which these medications hold significance, a holistic understanding of the nature of our reliance on antibiotics is needed. The aim of this study was to describe how antimicrobials intersect with life, livelihoods and health care for humans and animals in rural households in Uganda. METHODS: I employed a multi-sited ethnographic approach. To explore patterns of antibiotic use, I led a series of antibiotic surveys, enrolling 100 households in rural Tororo, 174 residents in urban Kampala and 115 pig and poultry farms in peri-urban Wakiso. In order to explore the significance of antibiotics and how antibiotic use is linked to wider social, economic and political trends in modern Uganda, I carried out ethnographic fieldwork in rural Tororo district in eastern Uganda over 14 months. I conducted participant observations, participant feedback meetings, and health worker interviews within homesteads, private clinics, government health centres, veterinary drug shops and animal markets. I compared findings from the research in Tororo with parallel ethnographic research, which I supervised over 10 months, in an informal settlement in Kampala and among pig and poultry farmers in peri-urban Wakiso. FINDINGS: Antibiotics were used frequently across the study sites, although the types and volume of antibiotics used by residents and farmers varied widely between the rural Tororo, urban Kampala and peri-urban Wakiso. Social and economic factors that shaped antibiotic use included the imperative to take opportunities and the discourse of betterment in today’s modern Uganda society, the insecurities that people encountered in their everyday lives and availability of resources and professional and patient expectations in health care settings. Antibiotic use was one of the ways that people took opportunities in a landscape where clinical research and humanitarian projects presenting medicines among other opportunities have become a way for people to better themselves for decades. With a vision to transform Uganda into a modern, independent, resilient and self-sustaining economy, Ugandans are persistently encouraged to take up opportunities availed through government and non-governmental programmes. This taking-of-opportunities had become an end in itself. In this context, the insecurity in peoples’ everyday lives which drives antibiotic use, was reinforced by the pervasive rhetoric of opportunity. In lower-level health facilities in Tororo where ‘care’ was characterized by delivery of medicines, clinical practice was shaped by availability of resources, and professional and patient expectations, as much as by the clinical guidelines. Clinical guidelines were present, and known in the health facilities, but seemed to co-exist with clinical practice rather than dictate it. CONCLUSIONS: Antibiotic use is central to the way people sustain everyday life in modern Uganda. The contextual information reflecting the multiple dimensions and connections involved with antibiotic use, provided by this thesis contributes to a growing literature that connects pharmaceutical practices with national and global systems. This research provides insights that can inform locally relevant interventions seeking to optimize the use of antimicrobials and to curb AMR in Uganda and elsewhere.