The management of intermediate coronary lesions, defined by a diameter stenosis of 40% to 70%, continues to be a therapeutic dilemma for cardiologists. The 2-dimensional representation of the arterial lesion provided by angiography is limited in distinguishing intermediate lesions that require stenting from those that simply need appropriate medical therapy. In the era of drug-eluting stents, some might propose that stenting all intermediate coronary lesions is an appropriate solution. However, the possibility of procedural complications such as coronary dissection, no reflow phenomenon, in-stent restenosis, and stent thrombosis requires accurate stratification of patients with intermediate coronary lesions to appropriate therapy. Intravascular ultrasound (IVUS) and fractional flow reserve index (FFR) provide anatomic and functional information that can be used in the catheterization laboratory to designate patients to the most appropriate therapy. The purpose of this review is to discuss the critical information obtained from IVUS and FFR in guiding treatment of patients with intermediate coronary lesions. In addition, the importance of IVUS and FFR in the management of patients with serial stenosis, bifurcation lesions, left main disease, saphenous vein graft disease, and acute coronary syndrome will be discussed.