microRNAs (miRNAs) are short (~22 nucleotides), non-coding, single-stranded RNA molecules that regulate the expression of target genes by partial sequence-specific base-pairing to the targeted mRNA 3′UTR, blocking its translation, and promoting its degradation or its sequestration into processing bodies. miRNAs are important regulators of several physiological processes including developmental and metabolic functions, but their concentration in circulation has also been reported to be altered in many pathological conditions such as familial hypercholesterolemia, cardiovascular diseases, obesity, type 2 diabetes, and cancers. In this review, we focus on the role of miRNAs in lipoprotein and lipid metabolism, with special attention to the well-characterized miR-33a/b, and on the huge potential of miRNAs for clinical application as biomarkers and therapeutics in the context of cardiometabolic diseases.