Clinical drug trials have traditionally focused on younger, healthier participants with less comorbidities and excluded frail older adults due to concerns regarding their ability to tolerate and respond to treatments. However, with population ageing, drug trials are increasingly turning their attention to older, frailer people. The aim of this review is to provide an overview of how frailty was assessed in published studies related to clinical pharmacological trials, and on the interaction of frailty on the safety and efficacy of the treatments. We searched MEDLINE, EMBASE and Cochrane for studies published in English that focused on clinical drug trials in older people. The review showed that frailty has been increasingly and successfully applied into clinical drug trials, especially trials in patients with cardiovascular disease and cancer. In most of the studies in the review, frailty was assessed retrospectively. How frailty was treated in statistical regression models was not consistent among the studies. Frailty was treated as an ordinal variable (with different levels of frailty) or binary variable (frail/non-frail) using cut-offs in some studies, and as a continuous in some other studies. There was heterogeneity in the effect of frailty, depending on the disease and treatment type. The results of this review suggest that frailty should not be assumed to always attenuate treatment effects, and routine measurement of frailty in participants in clinical drug trials would improve our knowledge of the effect of treatment in the frail and identify those who have more or least to gain from treatment.