Cardiovascular disease is the leading cause of death and is also a major cause of disability worldwide. Indeed, even in well-treated patients for hypertension or dyslipidemia, there is still a high cardiovascular risk called residual risk. It is of utmost importance to identify the pathway leading from risk factors to cardiovascular disease to further improve stroke and myocardial infarction prevention. In this review, we presented some of experimental and epidemiological evidences suggesting that microbiota-host crosstalk is involved in this pathway and bridges the gap between cardiovascular risk factors, diet, and cardiovascular residual risk. We considered the 3 participants in this dialogue: the gut microbiota, the intestinal barrier, and bacterial translocation. We analyzed their relations with cardiovascular risk factors and cardiovascular diseases. Also, we presented some of therapeutic strategies aiming to control microbiota to further prevent cardiovascular disease and the take home messages that can be drawn for clinical practice.