This review focuses on microRNAs (miRs) in cardiac surgery, where they are emerging as potential targets for therapeutic intervention as well as novel clinical biomarkers. Identification of the up/down-regulation of specific miRs in defined groups of cardiac surgery patients can lead to the development of novel strategies for targeted treatment in order to maximise therapeutic results and minimise acute, delayed or chronic complications. MiRs could also be involved in determining the outcome independently of complications, for example in relation to myocardial perfusion and fibrosis. Because of their relevance in disease, their known sequence and pharmacological properties, miRs are attractive candidates for therapeutic manipulation. Pharmacological inhibition of individual miRs can be achieved by modified antisense oligonucleotides, referred to as antimiRs, while miR replacement can be achieved by miR mimics to increase the level of a specific miR. MiR mimics can restore the function of a lost or down-regulated miR, while antimiRs can inhibit the levels of disease-driving or aberrantly expressed miRs, thus de-repressing the expression of mRNAs targeted by the miR. The main delivery methods for miR therapeutics involve lipid-based vehicles, viral systems, cationic polymers, and intravenous or local injection of an antagomiR. Local delivery is particularly desirable for miR therapeutics and options include the development of devices specific for local delivery, light-induced antimiR, and vesicle-encapsulated miRs serving as therapeutic delivery agents able to improve intracellular uptake. Here, we discuss the potential therapeutic use of miRNAs in the context of cardiac surgery.