Cardiac resynchronization therapy (CRT) is an established therapy for patients with advanced heart failure and wide QRS intervals. Numerous single-center studies indicated that the assessment of mechanical dyssynchrony helps predict response to CRT. However, two multi-center studies disprove the idea that the conventional assessment of mechanical dyssynchrony is useful for CRT patient selection. The purpose of this review is to provide an overview of the conventional methods as well as three novel approaches (cross-correlation analysis, Fourier analysis of strain uniformity, and discoordination analysis) for dyssynchrony assessments and their potential usefulness in predicting response to CRT.