Biochemical monitoring of patients treated with antihypertensive therapy is recommended in order to identify potential adverse reactions to treatment. We aimed to review the literature investigating the nature of biochemical monitoring in adults treated in primary care with antihypertensive drugs. Specifically, we wished to establish (i) the proportion of patients with biochemical baseline testing prior to the initiation of antihypertensive therapy; (ii) the proportion of patients with biochemical monitoring after initiation of antihypertensive therapy; (iii) the patient characteristics associated with biochemical monitoring; (iv) the frequency of biochemical monitoring after the initiation of antihypertensive therapy; and (v) the relationship, if any, between biochemical monitoring and adverse patient outcomes. We searched MEDLINE, EMBASE and Google Scholar from 1948 to 31 December 2010 using a combination of text words and search terms. Retrospective and prospective cohort studies, cross-sectional studies, randomized controlled trials or quasi-randomized controlled trials, and audits of current clinical practice were included. Clinical trials, case reports and case series were excluded. Studies were included if they provided data on the proportion of patients treated with antihypertensive therapy in primary care who had any biochemical monitoring before or after the initiation of therapy. In total, 15 studies were included in our review, which used a wide variety of definitions of monitoring prior to and after the initiation of antihypertensive therapy. From 17% to 81% of patients treated with antihypertensive drugs had a baseline biochemical test and from 20% to 79% had any follow-up monitoring. In only 7 of the 12 studies that examined follow-up monitoring did more than half of the patients have any monitoring. Overall, this systematic review provides evidence that monitoring as recommended by published guidelines is not commonly undertaken. Only two studies were identified that examined patients with both baseline testing and follow-up monitoring. Omission of one or the other limits the ability to analyse the effect of treatment on electrolyte concentrations or renal function. There is limited research on the patient factors associated with monitoring and further work is required to determine the impact of monitoring on adverse patient outcomes. Important barriers to effective monitoring exist and this review emphasizes that these have not yet been overcome.