Several non-coding microRNAs (miRs) are implicated in the pathogenesis of obesity, metabolic syndrome, diabetes mellitus, atherosclerosis and cardiovascular disease. Some of these miRs are beneficial but others are hazardous. Silencing of the latter by antisense oligonucleotides has been attempted in animal models with promising results. However, the replacement of down-regulated beneficial miRs, by manufactured miR mimics, or increasing their expression is much more demanding and has several limitations. The treatment of cardiovascular diseases through miR manipulation shows potential, provided safety and cost effectiveness issues are considered carefully before implementation in humans.