Laser Speckle Contrast Imaging (LSCI) is a high-speed, wide-field optical imaging technique that enables real-time characterization of microvascular blood flow. This chapter provides a concise overview of LSCI’s core principles, tracing its development from simplified single-exposure approaches to more sophisticated models accounting for non-ergodic scattering. We highlight recent methodological progress—from refined theoretical models and specialized hardware configurations to novel computational strategies—all aimed at enhancing measurement accuracy, precision, and depth penetration. In addition, we examine emerging applications across multiple organ systems, including the brain, retina, kidney, and liver. These advancements underscore LSCI’s growing prominence in preclinical research and signal its potential for broader adoption in microvascular research.