Laser speckle contrast imaging (LSCI) has emerged as a powerful and widely used tool for real-time imaging of blood flow dynamics in a variety of animal models and recently in the clinical environment. LSCI has been rapidly adopted for studying physiological changes due to its simple instrumentation and its ability to quantify blood flow changes with excellent spatial and temporal resolution. Because measurements are limited to superficial tissues, LSCI is an ideal imaging method for intraoperative applications and can provide surgeons with immediate physiological information without extending the procedure time significantly. This chapter reviews the physics of LSCI and illustrates in vivo applications of imaging blood flow in the brain with an emphasis on clinical translation of the technique.