Cardiovascular disease (CVD) still being the most common cause of death in worldwide. In spite of development of new lipid-lowering therapies which optimize low-density lipoprotein cholesterol (LDL-c) levels, recurrence of CVD events implies addressing factors related with residual cardiovascular (CV) risk. The key determinants of residual CV risk include triglyceride-rich lipoproteins (TRLs) and remnant cholesterol (RC), lipoprotein(a) [Lp(a)] and inflammation including its biochemical markers such as high sensitivity C reactive protein (hs-CRP). On the other hand, unhealthy lifestyle habits, environmental pollution, residual thrombotic risk and the residual metabolic risk determined by obesity and type 2 diabetes (T2D) have a specific weight in the residual CV risk. New pharmacologic therapies and pathways are being explored such as inhibition of apolipoprotein C-III (apoC-III) and angiopoietin-related protein 3 (ANGPTL3) in order to explore if a reduction in TRLs and RC reduce CVD events. Therapeutic target of inflammation plays an attractive way to reduce the atherosclerotic process and to date, approved therapies as colchicine plays a beneficial effect in chronic inflammation and residual CV risk. Lp(a) constitutes one of the most residual CV risk factor due to linkage with CVD and aortic valve stenosis. New and hopeful treatments including antisense oligonucleotides (ASO) and small-interfering ribonucleic acid (siRNA) which interfere in LP(a) codification have been developed to achieve an adequate control in Lp(a) levels. This review points out the paradigms of residual CV risk, discus how we should manage their features and summarize the different therapies targeting each residual CV risk factor.