Pharmacists' roles are shifting away from medicines supply and the provision of patient education involving acute medications towards consultation-type services for chronic medications. Determining the cost effectiveness of pharmacist interventions has been complicated by methodological challenges. A critique of 31 economic evaluations carried out alongside comparative studies of pharmacist interventions published between 2003 and 2013 (12 from the UK, six from the USA) found a range of disease-specific and cross-therapeutic interventions targeting both patients and prescribers in a range of settings evaluated through a variety of study designs. Only ten were full economic evaluations, five of which were based on randomized controlled trials (RCTs). The intervention was usually quite well described, but the comparator was not always clearly described, and some interventions are very context specific due to the variability in pharmacist services available in different countries and practice settings. Complex multidirectional aims of most pharmacist interventions have led to many process, intermediate and longer-term outcomes being included in any one study. Quality of resource use and cost data varied. Most incremental cost-effectiveness ratios (ICERs) were generated from process indicators such as errors and adherence, with only four studies reporting cost per quality-adjusted life-year (QALY). Very few studies examined the effect of uncertainty, and methods used were not very clear in some cases. The principal finding from our critique is that poor RCT study design or analysis precludes many studies from finding pharmacist interventions effective or cost effective. We conclude with a set of recommendations for future study design.