Hypertriglyceridemia is frequent in diabetic and obese subjects, who are at increased risk for cardiovascular diseases (CVD). Increased triglycerides (TG) are a hallmark of atherogenic dyslipidemia, representing a marker of atherogenic small dense low-density lipoproteins (sdlDL). Importantly, non-fasting/postprandial TG measurements tend to be emphasized in clinical practice for the prediction of CVD, and TG-lowering agents (primarily fibrates) have a beneficial effect on atherogenic dyslipidemia, reducing TG-rich particles and ultimately lowering the production of sdlDL. The combination of omega-3 fatty acids and statins is also recommended, and widely used in clinical practice for subjects with hypertriglyceridemia. However, a consensus on the optimal clinical use of these pharmacological agents is not fully established yet, and additional large clinical studies are needed. It seems that there is a favorable association between fish consumption and mortality from CVD, but it remains to be confirmed by future trials. Finally, there are a number of novel therapies, such as those targeting microsomal transport protein and its inhibitors, which represent new promising option for treating subjects with hypertriglyceridemia.