Failure of coronary angiography (luminography) in prediction of future acute coronary syndromes has cast a shadow of doubt over the value of this old gold-standard technique. The fact that angiographically invisible or nonsignificant lesions cause the majority of acute coronary syndromes has driven scientists to develop new diagnostic methods. In this article, we review the ongoing worldwide research on both invasive techniques (such as intravascular angioscopy and colorimetry, ultrasound, thermography, optical coherence tomography, near infrared spectroscopy, Raman spectroscopy, fluorescence emission spectroscopy, elastography, magnetic resonance imaging [MRI] and spectroscopy, nuclear immunoscintigraphy, electrical impedance imaging, vascular tissue doppler, and shear stress imaging) and noninvasive techniques (such as MRI, contrast-enhanced MRI with and without immunolabeled agents, electron beam computed tomography, multi-slice spiral / helical computed tomography, and nuclear imaging, including positron emission tomography). Each of these techniques and their potential combination holds promise for characterization of plaques responsible for acute coronary syndromes, namely vulnerable plaque.