Globally, cardiovascular diseases (CVDs) are the number one cause of mortality. Approximately 18 million people died from CVDs in 2015, representing more than 30% of all global deaths. New diagnostic tools and therapies are eagerly required to decrease the prevalence of CVDs related to mortality and/or risk factors leading to CVDs. Oxylipins are a group of metabolites, generated via oxygenation of polyunsaturated fatty acids that are involved in inflammation, immunity, and vascular functions, etc. Thus far, over 100 oxylipins have been identified, and have overlapping and interconnected roles. Important CVD pathologies such as hyperlipidemia, hypertension, thrombosis, hemostasis and diabetes have been linked to abnormal oxylipin signaling. Oxylipins represent a new era of risk markers and/or therapeutic targets in several diseases including CVDs. The role of many oxylipins in the progression or regression in CVD, however, is still not fully understood. An increased knowledge of the role of these oxygenated polyunsaturated fatty acids in cardiovascular dysfunctions or CVDs including hypertension could possibly lead to the development of biomarkers for the detection and their treatment in the future.