Accumulating evidence suggests that day-by-day blood pressure (BP) variability assessed using self-measurements by patients at home (HBPV) provides useful information beyond that of average home BP. This systematic review summarizes the current evidence on day-by-day HBPV. A systematic literature search (PubMed) revealed 22 eligible articles. Independent prognostic value of day-by-day HBPV for cardiovascular events and total mortality was demonstrated in two outcome studies, whereas novel indices of variability had minimal or no independent prognostic ability. Although findings are not consistent among the studies, the evidence suggests that HBPV has an independent role in the progression of preclinical cardiac, arterial and renal damage and is affected by age, gender, average BP and heart rate level, antihypertensive treatment, antihypertensive drug class and other factors. However, there is large diversity among the available studies in the home BP monitoring protocols, the indices used to quantify HBPV and the end points selected for evaluation. Overall, these preliminary data largely based on heterogeneous studies indicate an important and independent role of day-by-day HBPV in the pathogenesis of hypertension-induced cardiovascular damage. Yet, fundamental questions remain unanswered, including the optimal variability index, the optimal home monitoring schedule required, the threshold that defines increased HBPV and the impact of treatment-induced variability change on organ damage and cardiovascular events. Until these questions are adequately addressed in future studies, HBPV should largely remain a research issue with limited practical value for individual patients.