Plastic consumption has experienced a significant increase in the past decade, resulting in the annual production of 400 million tons. These plastics have the potential to break down into microplastics, which are particulates that are less than 5 mm in diameter. Microplastics are intentionally manufactured, such as microbeads found in cosmetics and personal care products, or through plastic degradation. These particles are now ubiquitous, even in remote regions like the Arctic. They can penetrate the human body through three exposure pathways, i.e., airborne inhalation, oral ingestion of contaminated food and water, and dermal absorption through skin contact. Their presence has been found in various body parts such as the brain, heart, and lungs. In vitro and in vivo studies have linked microplastics to liver dysfunction, gut dysbiosis, urinary tract disorders, respiratory and neurological diseases, and reproductive and developmental toxicity. Microplastics can accumulate in cardiomyocytes (cardiac muscle cells), resulting in oxidative stress and may cause cardiac injury and fibrosis. Their presence has also been associated with atherosclerotic plaques in the carotid arteries, increasing the risk of stroke and overall mortality. The presence of microplastics is also associated with atherosclerosis in coronary arteries, and increased concentration is associated with a high risk of coronary artery disease (CAD) severity. This chapter provides an overview of microplastic production and its various exposure pathways penetrating the human body. The toxicity and mechanisms (oxidative stress and DNA damage, inflammatory and immune responses) through which microplastics cause disease pathogenesis in different organs of the body are discussed in detail, with a particular emphasis on cardiovascular diseases (CVDs), which cause the highest mortality worldwide. The chapter also discusses the studies conducted to decipher the presence of microplastics and the severity of CVDs. However, a causal relationship between microplastic concentration and human disease severity is yet to be established.