Given that the variation in how regional adipose tissue handles and stores excess dietary energy has substantial cardiometabolic implications, ectopic fat distribution might be an important predictor of cardiometabolic and vascular risk, in addition to overall obesity itself. Conceptually, ectopic fat depots may be divided into systemically acting fat depots and locally acting fat depots. Systemically acting fat depots include visceral fat, fat in the liver, muscle, or neck, and subcutaneous fat. Accumulation in the abdominal visceral area, compared with overall obesity, has an equally or more important role in the development of cardiometabolic risk. Fat depots in liver/muscle tissue cause adverse cardiometabolic effects by affecting energy metabolism. Fat depots in lower-body subcutaneous areas may be protective regarding cardiometabolic risk, by trapping remnant energy. Fat accumulation in the neck is a unique type of fat depot that may increase cardiovascular risk by increasing insulin resistance. Locally acting fat depots include pericardial fat, perivascular fat, and renal sinus fat. These fat depots have effects primarily on adjacent anatomic organs, directly via lipotoxicity and indirectly via cytokine secretion. Pericardial fat is associated with coronary atherosclerosis. Perivascular fat may play an independent role in adverse vascular biology, including arterial stiffness. Renal sinus fat is a unique fat depot that may confer additional cardiometabolic risk. Thus, ectopic fat depots may contribute to the understanding of the link between body composition and cardiometabolic risk. In this review, we focus on the role and clinical implications of ectopic fat depots in cardiometabolic and vascular risk.