Adherence to medication has been widely identified as a risk factor to the recurrence of Cardio Vascular Disease (CVD). Good adherence is associated with positive health outcomes and poor adherence to treatment actually increases the likelihood of suffering a recurrent CV event. A recent study further showed that low-risk, intermediate risk and high-risk patients with AMI in the year following discharge, present poor adherence rates to prescribed therapies: 61.5, 57.9 and 45.9 % respectively [1]. Supporting this finding, a previous meta-analysis also demonstrated that compliance with the medication was met only in 66 % of CVD cases [2]. The polypill approach, which combines several medicines that simultaneously control several risk factors or disease mechanisms in a single pill, is one of those strategies that has, in recent years, progressed in the CVD field [3]. The concept was introduced by Wald and Law in 2003, who described a fixed-dose combination strategy, containing six components, and claimed that the administration of this polypill to each individual over 55 years old would reduce the incidence of CVD by more than 80 % [4]. Since then, several polypill concepts have been proposed, including the ‘vaccination approach’, which refers to the use described by Wald and Law, as well as the use in primary and secondary CVD prevention. Polypills are typically defined as combination medication containing at least one blood pressure lowering (often multiple), one lipid lowering drug and frequently an antiplatelet agent. They are also referred to as Fixed Dose Combinations (FDC’s). As with most treatments, the benefits, as well as the drawbacks of the polypill, have been widely discussed. Some argued that the originally proposed estimated risk reduction potential of the polypill could be too optimistic and that many patients would remain undertreated. Concern about potential adverse effects related to some of the polypill’s monocomponents also exist, and it has been argued that side effects from one of the components could lead to discontinuation of treatment. This could then result in the loss of all the benefits of the other components included in the polypill. Nonetheless, despite these concerns, the potential of the polypill to improve the management of CVD risk factors has been recognised by several expert panels, including the WHO and the Combination Pharmacotherapy and Public Health Research Working Group, who consider research in this area an important breakthrough [5]. The currently available evidence shows that the use of polypills (defined as combination medication containing at least one blood pressure lowering and one lipid lowering drug) in patients with established disease or at high risk of developing CVD (i.e. those with established indications for polypill component medications – secondary prevention or high risk primary prevention) improves adherence to CVD preventive medications with consequent improvement in CVD risk factor levels [6]. The focus must now shift to implementing these drugs into clinical practice. Although controversies remain around usage based on single risk factor indications (or mass treatment), use in secondary prevention and high risk primary prevention populations is non-controversial and is the ‘low-hanging fruit’ for polypill usage [7].