Therapeutic drug monitoring (TDM) is commonly employed to optimize the dosing of certain drugs, including digoxin, aminoglycosides, theophylline, and phenytoin. Studies were reviewed in order to (a) evaluate the effect of TDM on the occurrence of toxic drug reactions (TDRs) and (b) identify factors that may modify or invalidate the relationship. In 14 studies, monitored patients suffered fewer toxic drug reactions than nonmonitored patients (odds ratio = 0.35, 95% confidence interval, 0.13 to 0.89). The average effect size was larger in studies that utilized a control group for comparisons rather than a before-and-after study design. TDM appeared to be most beneficial for patients taking theophylline or digoxin. Issues that must be addressed in future TDM service evaluations include (a) study design, (b) adverse patient selection, (c) insufficient sample size, (d) incomplete or inconsistent description of the TDM service, and (e) incomplete, inconsistent, or absent description of criteria for reporting TDRs.