This review article explores the challenges and controversies involved in accurately identifying and reliably quantifying coronary plaque over time through coronary computed tomography angiography (CCTA), particularly focusing on lipid-rich, low-attenuation plaques. It highlights significant variability in lipid-rich plaque measurements across studies, questioning their reliability for tracking biological plaque transformation in clinical practice. To address this issue, the review article proposes suggestions for serial CCTA plaque measurements, aiming for realistic goals for reproducible and meaningful serial plaque CCTA imaging. It also emphasizes the necessity of standardized, validated methods for quantitative plaque analysis and underscores the potential of phantom-based calibration to improve the reliability and consistency of serial plaque measurements in clinical practice.