The study aimed to synthesise qualitative studies of lay experiences of medicine taking. Most studies focused on the experience of those not taking their medicine as prescribed, with few considering those who reject their medicines or accept them uncritically. Most were concerned with medicines for chronic illnesses. The synthesis revealed widespread caution about taking medicines and highlighted the lay practice of testing medicines, mainly for adverse effects. Some concerns about medicines cannot be resolved by lay evaluation, however, including worries about dependence, tolerance and addiction, the potential harm from taking medicines on a long-term basis and the possibility of medicines masking other symptoms. Additionally, in some cases medicines had a significant impact on identity, presenting problems of disclosure and stigma. People were found to accept their medicines either passively or actively, or to reject them. Some were coerced into taking medicines. Active accepters might modify their regimens by taking medicines symptomatically or strategically, or by adjusting doses to minimise unwanted consequences, or to make the regimen more acceptable. Many modifications appeared to reflect a desire to minimise the intake of medicines and this was echoed in some peoples’ use of non-pharmacological treatments to either supplant or supplement their medicines. Few discussed regimen changes with their doctors. We conclude that the main reason why people do not take their medicines as prescribed is not because of failings in patients, doctors or systems, but because of concerns about the medicines themselves. On the whole, the findings point to considerable reluctance to take medicine and a preference to take as little as possible. We argue that peoples’ resistance to medicine taking needs to be recognised and that the focus should be on developing ways of making medicines safe, as well as identifying and evaluating the treatments that people often choose in preference to medicines.