Colesevelam is the newest bile resin with a unique chemical structure. It binds to bile acids with higher affinity than traditional bile acid sequestrants and has fewer gastrointestinal side effects and drug interactions. Colesevelam is safe and efficacious alone or in combination with HMG-CoA reductase inhibitors (statins) in reducing low-density lipoprotein cholesterol (LDL-C) levels. Despite this, the role of colesevelam in the treatment of hyperlipidemia remains limited, particularly in the face of new lipid lowering agents. As guidelines for cholesterol control become more stringent, the need to maximize therapeutic benefit through combination therapy will become increasingly more important. Colesevelam has a dose-sparing effect on statin therapy, potentially decreasing the risk of unwanted side effects or drug-drug interactions associated with statin use. This makes colesevelam a viable option for addition to a statin regimen when goal LDL-C levels cannot be achieved with a statin alone. Additionally, anecdotal reports indicate that colesevelam may have potential benefits in certain patient populations that cannot tolerate other lipid lowering therapies, including organ transplant recipients, cholestatic liver disesase, and end-stage renal disease. By recognizing the potential utility of colesevelam, clinicians can better manage those patients who are not able to tolerate first-line therapies.